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Welcome Message
Dear colleagues,
As president of the Asian Environmental Mutagen Association (AAEMS), I am pleased to welcome you
to the 7th Asian Conference on Environmental Mutagens (7th ACEM) and the 19th Conference of Chinese
Environmental Mutagen Society (19th CEMS) held in Qingdao on November 4-7, 2022.
With a theme of "Global Change and Environmental Genomic Health in Asia", the conference aims topromote research on the basic application and transformation of environmental mutagens and genomic
health in Asia and the Pacific Rim, and to develop and close to peer exchanges and cooperation within
the region. The conference was originally scheduled to be held in Qingdao in November 2021. However,
we are sorry that the conference had to be postponed until November 4-7, 2022 given the COVID-19
pandemic.
The Asia-Pacific region has assumed a critical role in the global economy. AAEMS is composed ofeight members of countries. Although every country has its own different cultural model and economic
development level, we face common environmental and health problems. The AAEMS was establishedto promote the continuous expansion and orderly conduct of research activities and exchanges in the fieldof environment and health.
The topics of the conference include not only traditional fields such as DNA damage repair, chemical
carcinogenesis, teratogenesis, and mutagenesis, but also some new fields such as exposure science andexposure omics, genomics and epigenetics, computer modeling, and bioinformatics. We hope that thisconference will attract the active participation of scholars from various fields of environment and healthsciences, especially young scholars and students, so as to inject fresh vitality into our field.
The Chinese Environmental Mutagen Society (CEMS) as the organizer of the conference, it has
made a great effort to organize the conference. In face of COVID-19, CEMS has repeatedly coordinatedwith various countries to adjust the time of conference, so that as many participants as possible canattend the conference. In view of China's current situation and policies in mitigating COVID-19, the conference plans to be held both online and offline. The vast majority of foreign representatives are likely toattend the conference online. However, we will still strive to ensure the best conference possible.
Finally, I wish this conference a great success.

Prof. Jia Cao
Chairman of ACEM/CEMS 2022
President of AAEMS
President of CEMS

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Congress Date and Venue
Date: November 5 - 6, 2022
Schedule outline:
November 5

November 6

Morning: Opening Ceremony & Keynote Lectures
Afternoon: Symposium
Morning: Symposium
Afternoon: Keynote Lectures & Closing Ceremony

Notice1. The keynote lectures and symposia in English will be held during November 5-6, 2022 online asscheduled and symposia in Chinese on-site has been postponed. The working language of the congress
is English.
2. ONLY the registered participants, speakers, and invited members are allowed to join the online
meeting. We will send the information to your mailbox. To join the meeting, please click Join Zoom
Meeting and type the unique passcode.

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Committees
Organizations
Asian Association of Environmental Mutagen Societies (AAEMS)
Chinese Environment Mutagen Society (CEMS)
Organizers
School of Public Health, Qingdao University
School of Public Health, Sun Yat-sen University
ChairmanJia Cao, President of Chinese Environmental Mutagen Society
Honorary Chairman
Shujun Cheng Yang Ke Dongxin Lin Masamitsu Honma (Japan)
Scientific Program Committee
Co-Chairs Wen Chen Tian-bao Zhang
Vice-Chairs Wei-dong Qu Wei Huang
Members
Lin Ao Sepideh Arbabi Bidgoli (Iran) Scott Byrne(Australia) Rui Chen
Zhihui Feng Amelia P. Guevara (Philippines) Aihua Gu Feng Hong
Wei Huang Yiguo Jiang Haidong Kan Kwon Wook Kang (Korea)
Geyu Liang Jianmeng Liu Huangyuan Li Yang Luan Wenjing Luo
Daru Lu Takehiko Nohmi (Japan) Shuangqing Peng Jingbo Pi
Radha Saraswathy (India) Malyn Ungsurungsie (Thailand) Yanhong Wei
Lijun Wu Yongjun Wu Dexiang Xu Yajun Xu Yuanyuan Xu
Masami Yamada (Japan) Xingfen Yang Dianke Yu Huidong Zhang
Rong Zhang
Organizing Committee
Co-Chairs Yuxin Zheng Weidong Hao
Vice-Chairs Yuepu Pu Jun Yang
Members
Guanghui Dong Sudi Gao Xiaoting Jin Jinyi Liu Qizhan Liu Yan Li
Qiao Niu Lanqin Shang Zhiwei Sun Jinglong Tang Baoen Shan
Qing Wang Xu Wang Xuetao Wei Shuang Wu Weidong Wu
Lihong Yin Wu Yao Aihua Zhang Lishi Zhang Xiulan Zhao
Jinping Zheng Zhijun Zhou Jiangbo Zhu"$&.$&.4

Program at a glance
Program Overview
Saturday, November 5, 2022
8:40-9:00

Opening Remarks

9:00-10:40

Keynote Lecture (KL)

10:40-10:55

Coffee Break

10:55-12:20

Keynote Lecture (KL)

12:20-14:00

Lunch Break

14:00-15:40

Symposium 1 (S1)

15:40-15:55

Coffee Break

15:55-17:30

Symposium 1 (S1)

Sunday, November 6, 2022



8:30-10:10

Symposium 2 (S2)

10:10-10:25

Coffee Break

10:25-12:05

Symposium 2 (S2)

12:05-14:00

Lunch Break

14:00-15:40

Keynote Lecture (KL)

15:40-15:55

Coffee Break

15:55-17:35

Keynote Lecture (KL)17:35-18:00

Closing Remarks

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Scientific Program
Opening Remarks/Keynote Lecture
Saturday, November 5, 2022
8:40-9:00

Opening Remarks
Chair: Prof. Jia Cao
Keynote Lecture (KL)
Chairs: Prof. Yuepu Pu, Prof. Weidong Qu
KL-1 How AI Can Beat Animal Testing at Finding Toxic Chemicals as Potential

9:00-9:50

Carcinogen.
Prof. Thomas Hartung (Johns Hopkins University, United States)
KL-2 A Body Map of Somatic Mutagenesis in Morphologically Normal Human

9:50-10:40

Tissues.
Academician Dongxin Lin (Chinese Academy of Medical Sciences, China)

10:40-10:55

Coffee BreakKL-3 The Future of Genome Research in Asia.

10:55-11:45

Prof. Masami Yamada (National Defense Academy, Japan)
KL-4 Applying an Integrative Approach for Risk Assessment on The Effects of

11:45-12:20

Chemical Mixtures in The Context of Real-Life Risk Simulation.
Academician Aristides M. Tsatsakis & Dr. Elisavet Renieri (University ofCrete, Greece)

12:20-14:00

Lunch Break"$&.$&.4

Symposium 1
Saturday, November 5, 2022
Symposium 1 (S1)
Chairs: Prof. Yankai Xia, Prof. Yuanyuan Xu
14:00-14:25

S1-1 DNA Adductomics in Human Tissues.
Prof. Haruhiko Sugimura (Hamamatsu University, Japan)
S1-2 Discovery of Functional Link between DNA Double-strand Break Repair

14:25-14:50

and the Early Transcriptional Response to the Sex Hormone.
Prof. Shunichi Takeda (Shenzhen University, China)
S1-3 Paternal Environmental Stress: From Sperm Epigenome to Offspring

14:50-15:15

Synapse Organization.
Prof. Yankai Xia (Nanjing Medical University, China)
S1-4 The Emerging Role of Nfe2l1 in Carcinogenesis: Action as and Beyond a

15:15-15:40

Transcription Factor.
Prof. Yuanyuan Xu (China Medical University, China)

15:40-15:55

Coffee BreakSymposium (S1)
Chairs: Prof. Nan Sang, Prof. Yanhong Wei
S1-5 Enhanced Gastric Tumorigenesis by Accumulation of Tumor-Associated

15:55-16:15

Macrophage in the Absence of Histamine Signal.
Prof. Ki Taek Nam (Yonsei University, Korea)
S1-6 Maternal Cadmium Exposure During Gestation Impairs Hippocampal

16:15-16:40

Neurogenesis and Cognition via Reducing Placenta-Derived Estrogen in Offspring.
Prof. Hua Wang (Anhui Medical University, China)
S1-7 The Cardiovascular Toxicity of Aryl Organophosphate Flame Retardants in

16:40-17:05

Embryonic Development.
Prof. Yanhong Wei (Sun Yat-sen University, China)
S1-8 Injury Target, Toxic Effect and Molecular Mechanism of Atmospheric

17:05-17:30

Pollutants from Coal-Burning Area.
Prof. Nan Sang (Shanxi University, China)"$&.$&.4

Symposium 2
Sunday, November 6, 2022
Symposium 2 (S2)Charis: Prof. Dianke Yu, Prof. Da Chen
8:30-8:55

S2-1 QSAR Prediction of Ames Mutagenicity.
Dr. Kiyohiro Hashimoto (Takeda Pharmaceutical, Japan)
S2-2 A Toxicity Pathway-Based Approach to Develop Adverse Outcome Path-

8:55-9:20

way.
Prof. Dianke Yu (Qingdao University, China)
S2-3 Development of Physiologically Based Pharmacokinetic (PBPK) Models
Within Bayesian Framework for Perfluorooctane Sulfonate (PFOS) and Its

9:20-9:45

Implications in the Derivation of Health-Based Toxicity Values.
Research Assistant Prof. Wei-Chun Chou (University of Florida, UnitedStates)

9:45-10:10
10:10-10:25

S2-4 Analytical Development for Environmental Exposome Research.
Prof. Da Chen (Jinan University, China)
Coffee BreakSymposium 2 (S2)Chairs: Prof. Yang Luan, Prof. Tiantian Li
S2-5 Metabolic Mechanisms and Toxic Effects of Polycyclic Aromatic Hydro-

10:25-10:50

carbons Regulated by CYP Enzymes Under Combined Pollution.
Associate Prof. Kai Luo (Southeast University, China)
S2-6 Applying Multi-Omics Approach to Reveal the Lung Cancer Biomarker.

10:50-11:15

Associate Prof. Ting Xiao (Chinese Academy of Medical Sciences and Peking
Union Medical College, China)
S2-7 Airborne PM2.5 Exposome and Cardiovascular Health: A Population-based

11:15-11:40

Integrated Methodology Establishment and Application.
Prof. Tiantian Li (Chinese Center for Disease Control and Prevention, China)
S2-8 Integrated-Studies Interpreted Oligophagous Butterfly Tolerate to Strong

11:40-12:05

Mutagen Aristolochic Acids.
Prof. Yang Luan (Shanghai Jiao Tong University, China)

12:05-14:00

Lunch Break"$&.$&.4

Keynote Lecture/Closing Remarks
Sunday, November 6, 2022
Keynote Lecture (KL)
Chairs: Prof. Shuangqing Peng, Prof. Jun Yang
KL-5 Effects of Circulating Small Extracellular Vesicle on Cancer Metastasis
14:00-14:50

and Chemoresistance.
Prof. Keon Wook Kang (Seoul National University, Korea)
KL-6 Air Pollution Exposure Mitigation and Health Intervention: Insights from

14:50-15:40

Source-Specific Cardiorespiratory Impairments.
Prof. Wei Huang (Peking University, China)

15:40-15:55

Coffee BreakKL-7 IARC Monographs on the Identification of Carcinogenic Hazards to

15:55-16:45

Humans.
Dr. Federica Madia (The International Agency for Research on Cancer(IARC), France)

16:45-17:35

KL-8 DNA Demethylation and Environmental Health Effects.
Prof. Hailin Wang (Chinese Academy of Sciences, China)
Closing Remarks
17:35-18:00



Chair: Prof. Jia Cao

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Introduction of Invited Speakers (Keynote Lecture)

KL-1
How AI Can Beat Animal Testing at Finding Toxic Chemicals as Potential Carcinogen.
Prof. Thomas HartungJohns Hopkins University, United States

Biography
Thomas Hartung, MD, PhD, is the Doerenkamp-Zbinden-Chair for Evidence-based Toxicology in the
Department of Environmental Health and Engineering at Johns Hopkins Bloomberg School of Public
Health, Baltimore, with a joint appointment at the Whiting School of Engineering. He also holds a joint
appointment for Molecular Microbiology and Immunology at the Bloomberg School. He is adjunct affiliate professor at Georgetown University, Washington D.C.. In addition, he holds a joint appointment as
Professor for Pharmacology and Toxicology at University of Konstanz, Germany. He also is Director ofCenters for Alternatives to Animal Testing (CAAT, http://caat.jhsph.edu) of both universities. CAAT hosts
the secretariat of the Evidence-based Toxicology Collaboration (http://www.ebtox.org) and manages
collaborative programs on Good Read-Across Practice, Good Cell Culture Practice, Green Toxicology,
Developmental Neurotoxicity, Developmental Immunotoxicity, Microphysiological Systems and Refinement. As PI, he headed the Human Toxome project funded as an NIH Transformative Research Grant andthe series of annual Microphysiological Systems World Summits starting in 2022 by 52 organizations. He
is Field Chief Editor of Frontiers in Artificial Intelligence. He is the former Head of the European Commission’s Center for the Validation of Alternative Methods (ECVAM), Ispra, Italy, and has authored morethan 620 scientific publications with more than 41,000 citations (h-index 105). His toxicology classes on
COURSERA had more than 15,000 active learners.

Abstract
A number of high-content and high-throughput technologies as well as the curation of databases of legacy
data and scientific publications have made big data in toxicology available in recent years. Machine learning (artificial intelligence, A.I.) allows to mine these data and make “big sense” from these big data
providing novel tools to complement risk assessments. We created a large toxicological data base from

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the European Chemical Agency (ECHA) extracting using linguistic search engines into a structured,machine readable and searchable database. Adding further public databases, a read-across-based structure
activity relationship (RASAR) was developed. Predictions were validated by cross-validation.
In collaboration with Underwriters Laboratories (UL), a global safety consulting and certificationcompany, a database with more than 10 million chemical structures (more than 300,000 of which annotated with biological and chemicophysical data and 80,000 with animal data). It took an Amazon cloud server
two days to analyze the similarities and differences between the 10 million chemicals to place them on amap, where similar chemicals are put close to each other, dissimilar ones distant. Making use of 74 properties in a data fusion approach, random forest machine learning was applied in a five-fold cross-validation.
Applying this to 190,000 classified chemicals based on animal tests, 87% of the time the computer wascorrect. Notably, each prediction comes with an expression of certainty based on the constellation of data
available. The software was even better for finding toxic than non-toxic substances with 89% success—exceeding the 70 percent probability of animal tests to find a toxic substance again in a repeat animal test,
shown in a parallel analysis of the database. The software (the UL Cheminformatics Tool Kit) at this stage
predicts nine different hazard classifications, traditional testing for which consumes 57 percent of all
animals in safety testing in Europe, or about 600,000 animals per year.
The predicted endpoints include mutagenicity but other elements possibly contributing to an integrated strategy to replace the cancer bioassay seem possible. In the process of expanding the RASAR
approach to systemic toxicities, ongoing work is aiming also to predict directly the outcome of the cancer
bioassay with promising preliminary results. Other A.I. uses will be discussed.

KL-2
A Body Map of Somatic Mutagenesis in Morphologically Normal Human Tissues.
Academician Dongxin Lin
Chinese Academy of Medical Sciences, China

Biography
Dr. Dongxin Lin is professor and director of the Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union medical College. He is also
professor of Sun Yat-sen University Cancer Center. He is an academician of Chinese Academy of

"$&.$&.4Engineering. His major research interests are cancer genetics and genomics, focusing on the identificationof germline and somatic genomic alterations that are associated with the development and progression ofhuman cancers such as esophageal cancer and pancreatic cancer. He has published more than 300 research
papers in peer-review journals including Nature, Nat Genet, Nat Med, Nat Commun, Gastroenterology andCancer Res, with H-index of 88 in 2022.

Abstract
Somatic mutations occur naturally in normal cells during cell division. The accumulation of such mutations in normal tissues are associated with aging and disease. Numerous studies have shown that cancer
cells have a large somatic mutation burden, which can be attributable to the endogenous and/or exogenous
mutagens. We have performed a comprehensive genomic analysis of 1,737 morphologically normal tissue
biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions
were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy
number alterations were rarely detected, except for in tissues from the esophagus and cardia. Endogenous
mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues,
although they exhibit different relative activities. Exogenous mutational processes operate in multiple
tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter
resolution. In the esophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometers were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones
were microscopic in size and evolved independently, possibly restricted by local tissue microstructures.
Our study depicts a body map of somatic mutations and clonal expansions from the same individual.

KL-3
The Future of Genome Research in Asia.
Prof. Masami Yamada
National Defense Academy, Japan

Biography
After spending 27 years in National institute of Health Sciences, Professor Masami Yamada currently
teaches Chemistry, Biology and Genetic Engineering at National Defense Academy of Japan. Graduation
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from Osaka University Faculty of Pharmaceutical Sciences with a Master's degree in 1986, she trained in
microbial genetics and molecular biology using Escherichia coli under Professor Atsuo Nakata at the Institute of Microbial Diseases, School of Medicine, and wrote her degree thesis on the regulatory mechanismsof phosphate regulons, then received her Ph.D. degree. Soon after, she became a research staff in Divisionof Genetics and Mutagenesis of National Institute of Health Science, NIHS, in 1990. Together with Dr.
Takehiko Nohmi, she worked on the improvement of Ames tester strains and the development of the target
gene and its recovery system for transgenic mice used in genotoxicity testing. In 1995, she went to the UK
and spent one year at the Clare Hall Laboratories as an overseas fellow of Science and Technology Agency(at that time). She worked with Dr. Peter Karran on a mechanism to recognize cisplatin and DNA
cross-links by mismatch repair proteins, which resulted in a paper. After returning to Japan, she contributed to the discovery of translesion DNA polymerase in E. coli. She published nearly hundred papers listed
in SCOPUS and h-index is 27. Using genetic engineering techniques, she has constructed many strainsfrom standard tester strains for the Ames. Such strains are useful for research fields on environmental
mutagens. Strain requests come to her every year from domestic, Asia, Europe, North America, SouthAmerica, and other countries. She has been a member of the Japanese Environmental Mutagen and
Genome Society, JEMS, since she joined the NIHS, and was awarded a JEMS Encouragement Award in
1998. She has served as an editorial board member, councilor, and director, and has been theeditor-in-chief for the society’s journal, Genes and Environment since 2018. She served as Treasurer of theInternational Association of Environmental Mutagenesis and Genomics Society for 2013 - 2017. She isalso currently serving as President of JEMS and working to reform the Society.

Abstract
As President of JEMS, I would like to introduce three recent achievements in genome research in Japan:
First, Hawk-Seq, a new technology developed by Matsumura's group, that can systematically and moreaccurately detect mutations that may lead to cancer. Second, Totsuka's group has developed a powerful
method to identify cancer-causing environmental mutagens by combining adductome and mutation signatures. The third, identified by Suzuki's group, is an examination of the dangers of genome disruption leading to chromothripsis that may be caused by genome editing. Matsumura’s group (Kao Corporation,
Kawasaki) has developed a new methodology called Hawk-Seq, which uses next-generation sequencing(NGS) to directly detect mutagens that induce genome-wide mutations. This may help to understand mutagen-induced mutation signatures and ultimately, the relationships between mutagens and human cancer.
Since the frequency of mutations due to exposure to mutagens is very low, it is important toimprove
the sequencing accuracy of NGS to detect mutagen-induced mutations. Therefore, they developed an error
correcting sequencing (ECS) to reduce the error frequency in NGS analysis: which collects sequence"$&.$&.4
information from both strands of a dsDNA fragment and can distinguish between true mutations andsequence errors. The ECS reduced error frequency to about 1/107 for GC base pairs and 1/108 for AT basepairs. Hawk-Seq was also effective in elucidating 96D mutation signatures caused by mutagen exposureand a close association between mutagens and human cancers.
Totsuka's group (Nihon University & National Cancer Center Research Institute, Tokyo) identified the
etiology of frequently occurring esophageal cancer in the Ci Xian high-risk area of China by a combinationof adductome and mutation signature analyses. They collected surgical specimen of esophageal cancer
patients in the high-risk area and compared them with those from low-risk areas. The results suggested thatthe guanine adduct of N-nitrosopiperidine (NPIP) was the cause of esophageal cancer in the Ci Xian area.
They then analyzed the genome in esophageal cancer cells that developed in rats after NPIP administration.
A reasonable match was found in the mutation signature between the samples from the NPIP-treated rats
and those from the cancer patients in Ci Xian mentioned above. Finally, I will address the concerns of
Suzuki's group (National Institute of Health Sciences, Kawasaki) about the “on-target” toxicity of the
Crisper/Cas9. Genome editing with CRISPR/Cas9 begins with double-stranded breaks, which are repaired
by non-homologous end joining in humans, during which mutations are likely to be introduced. Therefore,
concerns about genotoxicity have been mentioned for CRISPR/Cas9-based therapies. It has recently beenreported that chromothripsis has been observed in more than 50% of some cancer types. Suzuki et al. created “designed” translocations by genome editing. They found that about 1 to 2% of translocations together
with about 20 % of chromosome aberrations involving the targeted chromosomes immediately after
genome editing. These results suggest that the risk of genome editing is higher than expected. They warn
against the use of genome editing which induces chromothripsis that can lead to carcinogenesis in a single
event.

KL-4
Applying an Integrative Approach for Risk Assessment on The Effects ofChemical Mixtures in The Context of Real-Life Risk Simulation.
Academician Aristides M. Tsatsakis
University of Crete, Greece

Biography
Professor, Academician Aristidis Tsatsakis, PhD, ERT, DSc, FATS, DHonC, DHonC, DHonC, HonProf,FMRAS, FMWAS, is the Director of the Department of Toxicology and Forensic Sciences of the Medical
"$&.$&.4
School at the University of Crete. Prof. Tsatsakis has published well over 1000 articles, over 600 of themin ISI journals with more than 20,000 citations and on h-index 68. Prof. Tsatsakis has given over 200
keynote and plenary lectures in international congresses and has been the promoter and chair of numerous
Symposiums and workshops in International Forum. Dr. Tsatsakis studies and concept on RLRS (real-liferisks simulation) based on low dose combined long term exposures related to health issues, is a crucial
element and the central driving force for application of theory to practice the safety evaluations in 21st
century. Among many honorary titles: member of National Academy of Sciences of Russia and EUROTOX president (2014-2016). In December 2020, Prof. Tsatsakis was recognized as Highly Cited Researcher in the field of Pharmacology-Toxicology.

KL-4
Applying an Integrative Approach for Risk Assessment on The Effects ofChemical Mixtures in The Context of Real-Life Risk Simulation.
Dr. Elisavet Renieri
University of Crete, Greece

Biography
Dr. Elisavet Renieri (female), has a background in Biology (Department of Biology of the National andKapodistrian University of Athens) and holds a PhD in Toxicology (2019) related to human health risk
assessment for cumulative exposure to chemicals, which took place in the Centre of Toxicology Science& Research (CTSAR), Faculty of Medicine of the University of Crete. She is a researcher in CTSAR in
the field of mixtures risk assessment and has an additional scientific interest in the development and optimization of telomere length assessment as a phenotypic biomarker of effect for long term exposures. Since
early 2020 she is also a post-doctoral researcher in the HERACLES Research Center, involved with thedevelopment of systemic biology models with the use of omics. She is a European Registered Toxicologist(ERT) and a member of the Hellenic Society of toxicology.

Abstract
Real life risk simulation is often neglected in regulatory risk assessment. The paradigm shift of modern
toxicology aims to assess real life exposures, paying particular attention to exposures to low doses, combined and long-term exposures when considering associations to health impacts. Within this context, two"$&.$&.4
new approaches have been proposed for the risk characterization of single chemicals and chemical mixtures: The source related Hazard Quotient (HQS) and Hazard Index (HIS) and the adversity specific Hazard
Index (HIA). In order to account for the aggregated exposure, the Source Related HQ approach was developed (HQS) where HQS is the ratio of the exposure from the specific source of interest to the respectedreference values. The HQS, before being compared to the reference dose, are adjusted by a correction
factor, in order to simulate aggregated exposure. A correction factor is calculated based on the permitted
exposure contribution from the specific source to the permitted aggregated exposure. Additionally, in orderto overcome limitations related to the classical HI approach where chemical specific ADIs that do notcorrespond to the same critical effect are used, an alternative approach of the HIA is presented. The calculation of the HIA is based on an analysis of the individual critical effects, in order to derive the critical effectand a risk characterization for the whole mixture. Case studies with the applied methodologies are alsopresented and critical overview of the current regulatory status is discussed.

KL-5
Effects of Circulating Small Extracellular Vesicle on Cancer Metastasis andChemoresistance.
Prof. Keon Wook Kang
Seoul National University, Korea

Biography
Professor, Dr. Keon Wook Kang is the Director of BK21 education and research program of the College of
Pharmacy, Seoul National University. In addition, Professor Kang served as the Vice Dean of the Collegeof Pharmacy at Seoul National University (2017-2019) and the Vice Chair of the Admissions Headquaterat Seoul National University (2020-2022). Dr. Kang obtained his bachelor's degree from the College of
Pharmacy, Seoul National University, and his Master's and Ph.D. degrees from the same university in 1995
and 1999, respectively. After obtaining his doctorate, he worked as a postgraduate researcher at New Drug
Development Research Center, SNU until 2001, and moved to University of California, Irvine as a postgraduate researcher and Research Associate until 2003. Dr. Kang published over 190 articles in SCI journals since becoming a faculty in 2003, and their SCOPUS H-index is 47. Dr. Kang's recent major research
themes are the following two fields. The first is to identify the cell-cell interactions involved in the malignant process of cancer and external factors affecting it, and the second is to evaluate the relationship"$&.$&.4
between the genetic variation and disease progression in patients with chronic liver metabolic diseases. He
is now the secretary-general of the Korean Society of Toxicology and Environmental Mutagenesis, and thechair of the scientific committee of the Korean Society of Pharmaceutical Sciences.

Abstract
Extracellular vesicles (EV) in the tumor microenvironment have emerged as crucial mediators that
promote proliferation, metastasis, and chemoresistance. However, the role of circulating small EVs (csEV)
in cancer progression remains poorly understood. In this study, we report that csEV facilitate cancer
progression and determine its molecular mechanism. csEVs strongly promoted the migration of cancer
cells via interaction with phosphatidylserine of csEVs. Among the three TAM receptors, TYRO3, AXL,
and MerTK, TYRO3 mainly interacted with csEVs. csEV-mediated TYRO3 activation promoted migration and metastasis via the epithelial-mesenchymal transition and stimulation of RhoA in invasive cancer
cells. Additionally, csEV-TYRO3 interaction induced YAP activation, which led to increased cell proliferation and chemoresistance. Combination treatment with gefitinib and KRCT-6j, a selective TYRO3 inhibitor, significantly reduced tumor volume in xenografts implanted with gefitinib-resistant non-small celllung cancer cells. The results of this study show that TYRO3 activation by csEVs facilitates cancer cell
migration and chemoresistance by activation of RhoA or YAP, indicating that the csEV/TYRO3 interaction
may serve as a potential therapeutic target for aggressive cancers in the clinic. We further identified apotent and highly selective TYRO3 inhibitor, and explored the role of TYRO3 from the immuno-oncological point of view. Blockade of TYRO3 boosts anti-tumor immune responses in both the tumor-draining
lymph nodes (TdLNs) and tumors in MC38-syngeneic mice models. Moreover, the combination of
TYRO3 inhibitor and anti-PD-1 therapy exerts significant synergistic anti-tumor effects in anti-PD-1
non-responsive 4T1-syngeneic mice model. These findings demonstrate that csEVs are a novel driver inmigration and survival of aggressive cancer cells via TYRO3 activation, and suggest potential usefulness
of TYRO3 targeting strategy to handle aggressive cancer. This work was supported by supported by the
National Research Foundation of Korea (NRF) grant funded by the Korea government (2021R1A2C2093196(K.W. Kang)).

"$&.$&.4

KL-6
Air Pollution Exposure Mitigation and Health Intervention: Insights from
Source-Specific Cardiorespiratory Impairments.
Prof. Wei Huang
Peking University, China

Biography
Prof. Huang received her doctorate degree in Environmental Health at Harvard T.C. Chan School of Public
Health in 2003, and then worked at the Health Effects Institute overseeing air pollution and health studies
in Asia between 2003-2007. She joined Peking University in 2008, and now is a faculty member in the
Department of Occupational and Environmental Health at Peking University of Public and serves as the
Deputy Director of Peking University Institute of Environmental Medicine. Her research interests include
air pollution exposure assessment, biological effects and risks of environmental exposures, and healthintervention policy. She has served on multiple advisory panels and as working group members for theWorld Health Organization, International Agency for Research on Cancer, China Ministry of Ecology andEnvironment. She also serves as the co Editor-in-Chief for International Journal of Hygiene and Environmental Health (IJHEH), Associate Editor for Science of the Total Environment (STOTEN), and Editorial
Board Member for Environmental Epidemiology in recent years. She is the Chair of Youth Committee ofChina Environmental Mutagen Society, and active Committee Members of International Society of Environmental Epidemiology (ISEE) and International Federation of Gynecology and Obstetrics (FIGO).

Abstract
In two longitudinal panels with repeated measurements, we observed that ambient air pollution significantly associated with cardiometabolic abnormalities in healthy adults and patients with chronic obstructive
pulmonary disease (COPD). In healthy subjects, ambient particulates in small size fractions (particulate
PDWWHULQGLDPHWHUȝP>302.5] and number concentrations of particles in sizes of 5 to 560 nm) andtraffic-related pollutants (black carbon, nitrogen dioxide, and carbon monoxide) were observed in associations with abnormalities of cardiac repolarization and hemodynamics, as well as heightening responses ofatherosclerotic vulnerable plaque, thrombogenicity, myocardial damage, and vascular and systemic"$&.$&.4
immune inflammation. In terms of metabolic health, air pollutant concentrations were closely related toworsening metrics of high-density lipoprotein functionality, proatherogenic lipoproteins, insulin resistance, and amino acid metabolism. For COPD patients, exposure to traffic-related air pollutants could
prompt the genesis of large and small airway dysfunctions, along with elevation of cardiac injury, vascular
calcific potential, airway/systemic inflammation and oxidative stress. Collectively, combustion-derived
particulate organic matters, particularly originating from traffic emissions and coal burning, were significantly associated with adverse cardiorespiratory effects in both healthy and COPD subjects. Further, we
conducted two systematic reviews funded by the WHO on the efficacy of short-term intervention at personal-level against air pollution. Results from the identified intervention studies showed that indoor portable
air cleaner uses could contribute to some reductions in indoor PM concentrations, however, which
remained well above WHO Global Air Quality Guideline Levels particularly in areas with high outdoor air
pollution concentrations, and some beneficial changes were observed on cardiovascular health but withmuch limited evidence on respiratory health. In summary, our findings can serve as mechanistic demonstration linking potential detrimental cardiorespiratory effects of source-specific emissions, and provide
insights on air pollution intervention priorities by calling for continuing efforts to reduce PM from combustion emissions.

KL-7
IARC Monographs on the Identification of Carcinogenic Hazards to Humans.
Dr. Federica Madia
The International Agency for Research on Cancer (IARC), France

Biography
Federica Madia, PhD, MS is a senior toxicologist within the Monographs programme of the Evidence Synthesis and Classification Branch of the International Agency for Research on Cancer (IARC). She isprimarily supervising the mechanistic aspects of IARC Monographs, including the application of the key
characteristics of carcinogens. Before she served as a scientific officer for nine years at the European Commission’s Joint Research Centre (JRC). There, she contributed to the activities aimed at the development

"$&.$&.4
of novel approaches to testing human systemic toxicity endpoints, in particular carcinogenicity and genotoxicity. In the previous 15 years, Federica was research scientist in Academia, working in various Institutions in US and Italy, at Leonard Davis School of Gerontology, University of Southern California (US),Mario Negri Sud, at the School of Pharmacy of University of Rome. Main area of research included biology of cancer and aging and age-related genomic instability plus further human toxicology and pharmacology research projects including mechanisms of flame retardants toxicity. She had also experience in thepharmaceuticals private sector and served as toxicology study director at CRO. Federica received a MS in
Biology, a PhD in Pharmacology and Toxicology and Post-grad Certificate in Ecotoxicology from University of Rome Sapienza, Italy.

Abstract
The IARC Monographs Programme is an international, interdisciplinary approach to carcinogenic hazard
identification operated by the International Agency for Research on Cancer (IARC), a specialized agencyof the World Health Organization. Its overall objective is to identify preventable causes of cancer. Its principal product is the serial publication IARC Monographs on the Identification of Carcinogenic Hazards to
Humans, which began in 1971 in accordance with a fundamental mission of the Agency: to prepare anddistribute authoritative information on human cancer, its causes, and its prevention. The Monographs have
evolved into what is considered as the World Health Organization’s encyclopedia on the environmental
and occupational causes of human cancer. Two or three volumes of the Monographs are prepared annually.
From 1971 through June 2022, more than 1036 unique agents and exposures have been reviewed and evaluated in 132 meetings, each meeting resulting in a volume of the IARC Monographs. Agents may be
re-evaluated as new information becomes available in the published scientific literature. The Monographs
have proven to be useful worldwide to scientists, public health authorities and the public.
Here, the objective and scope of the IARC Monographs Programme, general principles and procedures to scientific review and evaluations are presented as reported in the amended Preamble to the IARC
Monographs. This also includes a mention to the mechanistic discussion that has been restructured to more
explicitly analyze evidence for the key characteristics of carcinogens identified during the Volume 100
Monographs and two subsequent expert workshops. In addition, a summary of the resulting evidence on
the evaluation of cobalt, antimony compounds, and weapons-grade tungsten alloy from the recent Monograph vol 131 is reported.

"$&.$&.4

KL-8
DNA Demethylation and Environmental Health Effects.
Prof. Hailin Wang
Chinese Academy of Sciences, China

Biography
Dr. Hailin Wang obtained his BSc in Chemistry from Wuhan University in 1991 and his PhD from the
Dalian Institute of Chemical Physics, Chinese Academy of Sciences in 1997. He had done his post-doctoral research at the University of Alberta, Edmonton, Canada, and joined the Research Center for
Eco-Environmental Sciences, Chinese Academy of Sciences (Beijing) in December 2005, where he isProfessor of Bioanalytical Chemistry and Toxicology. He developed advanced analytical technologies(UHPLC-MS/MS, qPCR, genome-wide sequencing) for characterization and functional study of DNA
5-methylcytosine and its oxidation intermediates and DNA N6-methyladenine. He for the first time
showed the enhancement of genome-wide 5-hydroxymethylcytosine by nutrient vitamin C, revealing arole of vitamin C in the regulation of DNA modification, and his study established a direct linkage
among vitamin C, Tet dioxygenases, and DNA methylation. As a world-wide seminal work, he discovered new epigenetic DNA modification (N6-methyladenine) in high eukaryotes (Cell, 2015). He also has
his expertise in ultrasensitive analytical technologies (e.g., capillary electrophoresis-laser induced fluorescence polarization, single molecule fluorescence imaging, and UHPLC-MS/MS) for detection ofcarcinogenic DNA adducts and for study of DNA-repair proteins interactions. He published 250 peer-reviewed papers on leading journals, including Cell, Nature, Science, Cell Research, Pro Natl Acad Sci
USA, J Am Chem Soc, Cell Res, Cell Discovery, Nucleic Acids Res, EHP. He is a member of the editorialadvisory board in a number of scientific journals, e.g., GPB, DNA repair, Chem Res Toxicol, J Chromatogr A, J Separation Sci.

Abstract
DNA methylation at cytosine (5mC) as an important epigenetic marker regulates gene expression andrenders cellular identity, and is critically involved in genome imprinting, inactivation of X chromosome
and parasite elements, and documentation of epigenetic memory. DNA demethylation remarkably"$&.$&.4
contributes to the dynamics of 5mC in mammals and is critical for multiple biological processes, including
animal cloning,nuclear reprogramming, development, and highly locus-specific regulation of gene activities. DNA demethylation can be initiated by the oxidation of 5mC and the formation of 5-hydroxymethylcytosine (5hmC), which are catalyzed by ten eleven translocation (Tet) family dioxygenases. The formed
5hmC can be diluted by DNA replication, suggesting a passive DNA demethylation pathway. Moreover,the 5hmC can be further oxidized by Tet proteins to form 5-formylcytosine (5fC) and 5-carboxylcytosine(5caC), which can be excised by thymine DNA glycosylase (TDG) followed by the reintroduction of
unmethylated cytosine through the base-excision repair (BER) pathway. This is an important pathway for
active DNA demethylation. The radically altered methylation, as observed in replication-independent
demethylation of the paternal genome in zygotes, may complete within hours. Genome-wide mapping
analysis has shown a strong enrichment of 5hmC within exons and near transcription start sites (TSSs),pointing to a potential role in transcriptional regulation. Furthermore, impaired hydroxylation of 5mC has
been observed in myelodysplastic syndromes, hepatocellular cancers and gliomas. We showed that a
number environmental and nutrient molecules profoundly altered DNA demethylation, including vitaminC, redox-active quinones, heavy metals (e.g., nickel), pharmaceutics (e.g., anticancer anthracycline drugs),
and environmental endocrine disruptors (e.g., BPA and BPS). The associated DNA demethylation mechanisms were also explored. For example, we identified a new feedback circuit of ERa activation–DNMT-TET2-DNA hydroxymethylation pathway in ER+ breast cancer cells and uncovered a pivotal role of
TET2-mediated DNA hydroxymethylation in modulating BPA/BPS-stimulated proliferation. To ourknowledge, we for the first time established a linkage among chemical exposure, DNA hydroxymethylation, and tumor-associated proliferation. These findings further clarify the estrogenic activity of BPA/BPS
and its profound implications for the regulation of epigenetic DNA hydroxymethylation and cell proliferation.

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Introduction of Invited Speakers (Symposia)

S1-1
DNA Adductomics in Human Tissues.
Prof. Haruhiko Sugimura
Hamamatsu University, Japan

Biography
After finishing medical school and obtaining license for medical doctor in1982, Faculty of Medicine, theUniversity of Tokyo, Dr. Haruhiko Sugimura directly got in Graduate School, Faculty of Medicine, theUniversity of Tokyo. His mentor was Dr. Wataru Mori (later he became the president of the University ofTokyo). He was trained as a pathologist on anatomical pathology and was awarded Doctor of Medical
Science (Ph.D. equivalent) in 1986. His thesis was on acute or chronic liver disease. He became board
certificated pathologists in 1987 and has been listed for 45 years. He spent post-doctoral training in Japan(1987, Research Resident, Epidemiology Division, National Cancer Center Research Institute, Tokyo) andUSA (1988-1990, Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, NCI, USA). In
this period, he endeavored into the new discipline “molecular epidemiology of cancer” and work on genetic
polymorphism, DNA adducts, and cancer susceptibility. After three years of training in NCI, he once cameback as an Assistant Professor, Department of Pathology, the University of Tokyo, his alma mater, but soon
was invited to the 1st Department of Pathology led by Prof. Isamu Kino, a distinguished GI tract pathologist as an Associate Professor, Hamamatsu University School of Medicine (1991). Since then he served as
an Associate Professor (1991-1995), and Professor (1995-) of the same department (currently renamed as
Department of Tumor Pathology). The original intention of the late Prof. Kino is introduction of molecularbiology into pathology field, which Dr. Sugimura devoted himself with younger colleagues. He published
300 and more papers listed on PubMed and h-index is 78. He was awarded Japanese Pathology Award in2015 and the topic is expounded in his review “Susceptibility to human cancer: From the perspective of apathologist. (Pathol Int. 2016. PMID: 27216305)”. He has been an active member of AACR, JCA, and JSP
for years. He served as a vice director of Hamamatsu University of School of Medicine and a director of
the library of Hamamatsu University School of Medicine, 2020.4-2022.3. In May 2022 he was also
appointed as the 11th director of Sasaki Institute Sasaki Foundation, Tokyo which used to be a leading"$&.$&.4
institute of carcinogenesis (Drs. Tomizo Yoshida and Takaoki Sasaki). He has trained many international
students including Rwandan scientists.

Abstract
DNA modifications and adduct formations are thought to be essential incipience of mutations, ultimate
origin of carcinogenesis. There have been many excellent systems of experimental carcinogenesis andmechanistic information on covalent bonding of chemical carcinogen to the base of DNA, DNA damage
and repair, mispairing and mutation are available, from rodents to bacteria. The reality of humancarcinogenesis in this context, however, is still scarce. We have not yet had the whole steps of environmental carcinogenesis especially existence of involvement of DNA adducts in human though the recent
study of mutation signatures in tumors suggest specific mutation processes according to individual
carcinogens. In this presentation I will address the challenge in adductome approach in human tissues.

S1-2
Discovery of Functional Link between DNA Double-strand Break Repair andthe Early Transcriptional Response to the Sex Hormone.
Prof. Shunichi Takeda
Shenzhen University, China

Biography
Shunichi Takeda, M.D, Ph.D, is a Distinguished Professor of Shenzhen University School of Medicine,
Emeritus professor of Kyoto University, and worked as the Department of Radiation Genetics at Kyoto
University during 1998-2020. Dr. Shunichi Takeda has studied molecular mechanism of radiotherapy andchemotherapy of tumors by employing a reverse genetic approach using a chicken B lymphocyte line technique. Prof. Shunichi Takeda has published more than 270 SCI articles in high-profile journals such as
Nature, Cell, Immunity, EMBO J, Molecular Cell, PNAS, Cell Rep, with more than 18,000 citations andsingle paper have been cited more than 1500 times, H index: 74. Prof. Takeda has been invited to given
keynote lectures and oral presentations at more than 70 international conferences. Dr. Shunichi Takeda
studies DNA damage response and tumorigenesis, based on constructed more than 100 gene knockout cell

"$&.$&.4
lines. Among many honorary titles: International Senior Scientists, Outstanding Talent of Pearl River,
Member of International Expert Committee of Shenzhen University. He also works as the editorial board
member of Nucleic Acids Research (NAR), Cancer and DNA Repair.

Abstract
Sex hormones, androgen and estrogen, bind to their receptors (AR and ER) and control the expression ofmany target genes. Ligand-associated AR and ER bind to target genes as transcription factors at transcription regulatory sequences, including promoter and enhancer. Activated AR and ER strongly stimulate theproliferation of the epithelial cells in prostate and mammary glands, respectively. The transcriptional
response to sex hormones is achieved by the activation of topoisomerase II (TOP2) catalysis at promotersand enhancers. TOP2 catalyzes strand passage reactions, which involve the movement of one intact
double-stranded DNA duplex through a transient enzyme-bridged break in another (gated helix). TOP2
covalently bind to the 5’ end of this transient break and rejoin it through the intrinsic ligation activity ofTOP2. TOP2 often fails to rejoin, and resulting DNA double-strand breaks (DSBs) are called stalled TOP2
cleavage complexes (TOP2ccs). Stalled TOP2ccs are rejoined by the removal of 5’ TOP2 adducts followedby ligation by nonhomologous end-joining (NHEJ). The removal of TOP2 adducts is achieved by a few
parallel pathways involving ataxia telangiectasia mutated (ATM), tyrosyl DNA phosphodiesterase-2(TDP2), and Breast cancer susceptibility gene I (BRCA1).We revealed that physiological concentrationsof androgen and estrogen generate DSBs in breast and prostate epithelial cells when they are deficient ineither ATM, TDP2, or NHEJ. The DSB formation depends on functional AR and ER and requires TOP2.
The loss of ATM, TDP2, and NHEJ changes early transcriptional response to androgen and estrogen. The
data uncovered the previously unknown link between DSB repair and early transcriptional response.
Remarkably, a defect in ATM, TDP2, or NHEJ causes the overexpression of c-MYC oncogene in responseto androgen and estrogen in mice. We propose that the sex hormone induces TOP2-dependent DSBs attranscription regulatory sequences and a defect in DSB repair increases the risk of breast and prostate
carcinogenesis.

"$&.$&.4

S1-3
Paternal Environmental Stress: From Sperm Epigenome to Offspring Synapse
Organization.
Prof. Yankai Xia
Nanjing Medical University, China

Biography
Prof. Yankai Xia is the vice president of Nanjing Medical University and professor of Toxicology at Schoolof Public Health. He is the Deputy Director of International Joint Research Center for Environment andHuman Health, China and the PI of State Key Laboratory of Reproductive Medicine and Key Laboratoryof Modern Toxicology. He works on environmental exposure and reproductive health. He has published>280 peer-reviewed research articles. He has received numerous academic awards, including the Second
Prize of National S&T Progress Award. He was elected fellow of the International Society of Exposure
Science (ISES), Birth Cohort Consortium of Asia (BiCCA) and several Chinese academic committees.
Prof. Xia also acts as Associate Editor/Editor of several distinguished journals in the environmental field.

Abstract
Recently, paternal environmental stress has received increasing concern due to its potential adverse effects
on offspring health. However, the underlying mechanism remains elusive. Sperm acts as a critical memory
carrier that records paternal environmental stress through epigenetic changes such as DNA methylation,
histone modifications, and non-coding RNAs, thus resulting in heritable changes in gene expression.
Among various paternal environmental stresses, we focused on Glufosinate-ammonium (GLA), a widelyused herbicide with emerging concern over its reproductive toxicity. In our study, adult male C57BL/6J
mice were administered 0.2 mg/kg·day GLA for 5 weeks, and then copulated with female DBA/2 mice toobtain offspring. Neurobehavioral tests showed that paternal GLA exposure induced behavioral abnormalities including decreased social novelty, learning and memory in 5-week-old offspring. To uncover memorytransmission from father to offspring, we focused on epigenetic changes carried by sperm. After examination on fertility, testis histology and semen quality in the GLA group, we performed deep sequencing to
identify DNA methylation, transcriptionally active (H3K4me3 and H3K27ac) and repressive (H3K27me3


"$&.$&.4
and H3K9me3) histone modifications, and mRNA transcript levels in sperm. We found no significant
abnormality either on fertility, testis histology or semen quality-related indicators in GLA mice. Next
generation sequencing showed alterations of these epigenetic marks and extensive transcription inhibitionin sperm. Differential active marks were enriched at promoters and putative enhancers, while repressive
marks were mainly distributed at intergenic regions and introns. They were mainly enriched in pathways
related to synapse organization. When we zoomed in these regions, increased H3K4me3 overlaps
H3K27ac loci at the gene promoter of Phkg2, which was actively expressed in GLA sperm. Moreover,histology analysis showed that paternal GLA exposure decreased dendrite complexity and spine density inhippocampus and prefrontal cortex of 5-week- old offspring, indicating abnormal synapse organization.
These results suggested that GLA predominantly affected sperm epigenome and transcriptome, with little
effect on fertility, testis histology or semen quality. These changes in sperm epigenetic marks induced bypaternal GLA exposure might lead to the synapse organization abnormalities in hippocampus, thus explaining decreased memory in offspring. Further studies are still required to better understand the informationin sperm epigenome under paternal environmental stress, and its impact on offspring health.

S1-4
The Emerging Role of Nfe2l1 in Carcinogenesis: Action as and Beyond a Transcription Factor.
Prof. Yuanyuan Xu
China Medical University, China

Biography
Dr. Yuanyuan Xu received the PhD degree in China Medical University and did Postdoc research in
National Institute of Environmental Health Sciences, USA. Her research mainly focuses on mechanisms
underlying chemical carcinogenesis. She has over 60 publications in peer-reviewed academic journals,
such as Environ Health Perspect, Redox Biol and Free Radic Biol Med, and serves in editorial board of
Toxicol Appl Pharmacol and Regul Toxicol Pharmacol. Her research work won 7 awards for young scientist from the Society of Toxicology, USA and International Union of Toxicology. She is the Principal Investigator of three grants form National Science Foundation of China, and has been selected as the Pandeng
Scholar and Outstanding Young Scientist in Revitalization Talents Program in Liaoning Province.
"$&.$&.4

Abstract
Nuclear factor erythroid-2-related factor 1 (NFE2L1) is a well-known cap'n'collar protein family memberthat plays critical roles in regulating a wide range of essential cellular functions. This factor has also been
implicated in the pathogenesis of cancer development. Our previous studies have reported NFE2L1 acts as
a transcription factor in oxidative stress defense, inflammation, metabolism, and differentiation. In a recent
study, we investigated the role of Nfe2l1 in chemical carcinogenesis by using alveolar type II epithelial(ATII) cell-specific Nfe2l1 knockout (Nfe2l1 (ATII)-KO) mice treated with the lung adenocarcinoma
inducer urethane (Ure). Under basal conditions, Nfe2l1 (ATII)-KO mice showed no significant alteration in
the lung functions and tissue histology, while Nfe2l1 (ATII)-KO mice, both male and female, showed exacerbated lung tumor formation after Ure treatment. Immunochemical analysis found that the tumor was
SPC, a ATII cell marker, positive. KEGG pathway enrichment analysis of differential expressing genes inseparated ATII cells from the 7-week Ure-exposed lungs disclosed that cell cycle and DNA replication are
the top two pathways affected by Nfe2l1 knockout. Since Ure is a classic DNA mutagen, we tested DNA
GDPDJH LQ WKH OXQJ DIWHU DFXWH 8UH H[SRVXUH 0RUH Ȗ+$;VWDLQLQJ FHOOV ZHUH REVHUYHG LQ Nfe2l1(ATII)-KO mice. In line with the in vivo observation, different cell lines with Nfe2l1 knockdown showed
server DNA damage caused by chemical or physical DNA insults. ROS scavenger only partially rescued
DNA damage resulting from Nfe2l1 deficiency. Interestingly, PARP1, a key enzyme in DNA damage
repair, was suppressed in protein levels and activity in Nfe2l1-silenced cells in response to DNA damage.
mRNA levels of PARP1 were not significantly affected following knockdown of Nfe2l1, ruling out thepossibility that Nfe2l1 transcriptionally regulates PARP1 expression. However, PARP1 protein stability
was reduced by Nfe2l1 silencing, which could be reversed by the proteasome inhibitors. Then, we subjected PARP1-GFP MLE12 cells to UV laser-microirradiation to detect the effect of Nfe2l1 silencing on
PARP1 response. Nfe2l1 silencing markedly inhibited PARP1 localization at the DNA damage stripes evenwhen PARP1 were overexpressed. HADDOCK2.4 molecular docking prediction suggests the possible
interaction of these two proteins. Nuclear translocation of NFE2L1 was synchronized with increase in
PARP1 protein after DNA damage. Co-localization of NFE2L1 and PARP1 in response to DNA damage
was observed by immunofluorescence. Immunoprecipitation and immunoblotting analyses found the interaction the two proteins, which could not be abrogated by ethidium bromide. Post-translational modificationof PARP1 modulates stability and activity of this protein. Nfe2l1 silencing was found to increase the ubiquitination levels of endogenous PARP1 in response to DNA damage. Of note, the lower protein levels of
NFE2L1 in human lung adenocarcinoma were found as compared to non-tumor adjunct tissue. Collectively, these findings suggest that NFE2l1 may act as a tumor suppressor and uncover a previously unrecognized mechanistic link between NFE2L1 and PARP1 in the regulation of cellular response to DNA damage.
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S1-5
Enhanced Gastric Tumorigenesis by Accumulation of Tumor-Associated Macrophage in the Absence of Histamine Signal.
Prof. Ki Taek Nam
Yonsei University, Korea

Biography
Professor, Ki Taek Nam, D.V.M., PhD, AGAF, DKCLAM is Tenured Full Professor, Severance Biomedical Science Institute and the Director of the Dep. Of Laboratory Animal Resource, Yonsei Biomedical
Research Institute, Yonsei University College of Medicine. Prof. Nam has published well over 100 articles
as main authors including high impact journal such as J Am Chem Soc (2019), ACS Nano (2018, 2019),
Biomaterials (2017,2022), Angew Chem (2022), NPJ Precis Oncol (2022), Biosens Bioelectron (2022),
Cancer Lett (2020), Gastroenterology (2007, 2009, 2010, 2021), Gut (2004, 2012, 2022). Prof. Nam hasgiven over 70 keynote and plenary lectures in international congresses and has been the promoter and chairof numerous Symposiums and workshops in International Forum. Dr. Nam was trained as a Veterinarianwith special qualifications Veterinary Pathology and mouse pathology at Seoul National University. He
has broad research training in epithelial cancer biology and his studies focused on the induction of gastriccancer in rodent models. He has focused his research efforts on understanding mouse models for the originof metaplasia in the stomach and the mechanisms leading to induction of colon cancer. Among many
honorary titles: member of AMMRA (Asian Mutant Mouse Resource Association) publication committee
and vice president of KOREA Mouse Phenotyping Center. Prof. Nam was recognized as Highly Cited
Researcher in the field of Gasteroenterology–Tissues Stem cell- Toxicopathology.

Abstract
Histamine in the stomach is traditionally considered to regulate acid secretion but has also been reported toparticipate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore,
this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and inmaintaining stomach homeostasis. Here, we expand on this role using histidine decarboxylase knockout(Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice,
germ-free Hdc-/- mice and bone-marrow transplanted Hdc-/- mice. The stomach macrophage populations and"$&.$&.4
function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA seq analysis on Hdc+/+ and Hdc-/- stomach tissues.
Single-cell RNA-sequencing and flow cytometry of the stomach cells of Hdc-/- mice revealed alterations in
the ratios of three distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHCIIhighCD74high). Tissue macrophages of the stomach of Hdc-/- mice showed impaired phagocytic activity,
increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. This study
demonstrated the importance of histamine signaling in tissue macrophage differentiation and maintenanceof gastric homeostasis through the suppression of bacterial overgrowth in the stomach.

S1-6
Maternal Cadmium Exposure During Gestation Impairs Hippocampal Neurogenesis and Cognition via Reducing Placenta-Derived Estrogen in Offspring.
Prof. Hua Wang
Anhui Medical University, China

Biography
Prof. Hua Wang has long engaged in early-life exposure to environmental metals and adverse offspringoutcomes. He is a member of Asian Alliance for Arsenic and Health, Chinese Pharmacological Society,
Chinese Society of Toxicology, Chinese Environmental Mutagen Society. He is also a standing member ofYouth Committee and Epigenetic Toxicology Professional Committee of Chinese Society of Toxicology,
Professional Committees of Teratogenesis and Environmental stress and Health Damage in Chinese Environmental Mutagen Society, a Chairman of Health Toxicology Professional Committee of Anhui Preventive Medical Association, and a standing council of Anhui Provincial Environmental Mutagen Society. He
is also a peer reviewer in Redox Biology, Journal of Hazardous Materials, Environment International,
Science of the total Environment, Ecotoxicology and Environmental Safety, Toxicological Sciences, Journal of Endocrinology, Toxicology, etc.

"$&.$&.4

Abstract
Early-life exposure to environmental cadmium (Cd) is known to cause developmental disorders, yet theeffect and mechanism of gestational exposure to Cd on the offspring’s cognitive function remains unclear.
Placenta as a well-established target organ for Cd-impaired fetal development, its role in estrogen regulation and offspring cognitive function is unknown. Our in vivo experiments found that gestational Cd expoVXUHLPSDLUHGFRJQLWLYHIXQFWLRQLQDGXOWPDOHRIIVSULQJDFFRPSDQLHGZLWKORZHUHGȕHVWUDGLRO ( levels in the male fetal brain upon Cd exposure. Correspondingly, the expression of synapse-associatedproteins including brain-derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95)
and synapsin-1 were downregulated, which were reversed when supplemented with E2 hormone during
gestation. Further observation showed placental estrogen synthesis inhibition and general control
non-derepressible 2 (GCN2) signaling activation upon Cd exposure, whereas placental estrogen synthesis
could be restored through inhibiting GCN2 activity. Based on ovariectomy (OVX) of pregnant mice, we
confirmed that Cd exposure reduced E2 level in fetal brain via inhibited placental-derived estrogen synthesis. The aforementioned Cd-induced fetal brain injury and cognitive impairment in adult offspring weresignificantly alleviated when pregnant dams were supplemented with anti-stress agent N-Acetyl-L-cysteine. In summary, Cd disrupted placental-derived estrogen synthesis via activating GCN2 signaling, andthereby caused cognitive impairment in adult offspring mice. Our findings suggest that placental-derived
estrogen may be an effect marker of environmental toxicants-evoked cognitive dysfunction in adultoffspring, and suggest that environmental toxicants may affect the fetal brain development via placenta-fetal-brain axis.

S1-7
The Cardiovascular Toxicity of Aryl Organophosphate Flame Retardants in
Embryonic Development.
Prof. Yanhong Wei
Sun Yat-sen University, China

Biography
Dr. Wei is a professor of Toxicology at the Sun Yat-sen University. She is dedicated to studying the adverse
health effects of environmental chemicals on the cardiovascular system and development. She received her"$&.$&.4
doctorate in Ecotoxicology from Chinese Academy of Sciences in 2008 and was a postdoctoral fellow at
the Johns Hopkins University from 2008 to 2016. Dr. Wei is the vice-chair of the Committee of Biochemistry and Molecular Toxicology in Chinese Society of Toxicology and the vice-chair of the Youth Committeeof Chinese Environmental Mutagen Society. She is currently an officer in the Cardiovascular Toxicology
Specialty Section of the Society of Toxicology. She published 27 peer-reviewed articles in SCI-indexed
journals, including PNAS. She acts as a principal investigator in three general programs supported by the
National Natural Science Foundation of China. She serves in the editorial boards of the Environmental
Pollution and the Archives of Toxicology.

Abstract
As brominated flame retardants are regulated and phased out worldwide, organophosphorus flame retardants (OPFRs) are becoming a popular alternative. As such, OPFRs’ hazardous effects on the environmentare becoming a growing concern. The increasing production and application of aryl organophosphate
flame retardants (Aryl-OPFRs), the typical non-halogenated flame retardants, give rise to the severe andworsening environmental impacts. Cardiovascular system is the main target of Aryl-OPFRs, which exerts
the stronger cardiovascular toxicity than alkyl organophosphate flame retardants in zebrafish. Cardiovascular system, especially blood vessels which consist of arteries, veins, and capillaries, is highly heterogenous. Exposure to xenobiotics leads to distinct cellular responses and regulatory fashions in various typesof blood vessels in all kinds of tissues. However, the characteristics of the adverse effects on the cardiovascular system and the underlying mechanisms by Aryl-OPFRs exposure are poorly understood. Here, wedevelop a deep learning-based quantitative framework to characterize vascular profiles in Tg (fli1a:eGFP)
zebrafish larvae by exploiting high-resolution fluorescence images from high-content screening. Using theframework, we analyzed morphological features of whole trunk blood vessels as well as the cerebral
vasculature and quantitated vascular disruptions caused by Aryl-OPFRs, Alkyl-OPFRs, BFRs, and theemerging FRs. The results showed that chemical insults led to heterogeneous cardiovascular patterns manifested by 34 architecture indices, and the common cardinal vein was the most affected vessel. In the quantification of vascular lesions, tert-butylphenyl diphenyl phosphate scored highest in Aryl-OPFRs. The
average score of Aryl-OPFRs was higher than that of Alkyl-OPFRs. We selected BDP for further investigation of intergenerational toxicity in cardiovascular development. The results showed that parental exposureWRQJ/WRȝJ/%'3OHGWRYDVFXODUGLVUXSWLRQVLQWKHRIIVSULQJV7KLVVWXG\H[WHQGVRXUNQRZOHGJH
of OPFR’s cardiovascular toxicity. More importantly, the findings will contribute to the identification ofearly responses, characterization of toxicity and the health risk assessment of Aryl-OPFR.


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S1-8
Injury Target, Toxic Effect and Molecular Mechanism of Atmospheric Pollutantsfrom Coal-Burning Area.
Prof. Nan Sang
Shanxi University, China

Biography
Sang Nan, professor, now works in Research Center of Environment and Health, College of Environmental and Resource, Shanxi University. She is the winner of National Natural Science Foundation-Outstanding Youth Foundation, and also received a number of awards, including Baogang excellent teacher award
and Huo Yingdong young teacher award. She has been engaged in environmental toxicology and environmental health for a long time, especially focusing on the toxicology and health effects of air pollution. She
has more than 100 papers have been published in international journals in the field of environmental toxicology and environmental health, including Environmental Health Perspectives, Environmental Science& Technology, Toxicological Sciences, etc. She acts as associated editor of Journal of Hazardous Materials and editorial board member of Science of The Total Environment.

Abstract
Our country is experiencing complex atmospheric pollution, and there are many challenges in clarifying
the health risk of atmospheric pollution, especially discriminating toxic component, revealing effect andmolecular mechanism, and finding offspring outcome. Focusing on “injury target, toxic effect and molecular mechanism of main atmospheric pollutants”, we conducted long and systematic studies and obtained
the following innovative results. 1) SO2 inhalation caused heart injury through free radical accumulation,
mitochondrial dysfunction and lipid metabolism perturbation, the damage different from that of traditional
respiratory system. 2) Maternal NO2 exposure reduced the methylation level of interleukin-4 (Il4) gene,promoted the imbalance of immune factors Th1/Th2 differentiation in offspring, the novel mechanism for
cardiopulmonary injury in early life and disease susceptibility change in later life. 3) PM2.5 exposure stimuODWHGQHXURLQIODPPDWLRQGRZQUHJXODWHGPL5SH[SUHVVLRQDQGHOHYDWHGȕVHFUHWDVHDFWLYLW\WKH
new pathway for resulting in neurodegenerative diseases. 4) The inorganic sulfate in particulate matter
regulated E-cadherin level by affecting methylation level, and then led to epithelial-to- mesenchymal transition and finally promoted the progression of lung cancer. Our findings provided scientific support for
toxic identification, risk management and prevention and therapy of atmospheric pollutants.
"$&.$&.4S2-1
QSAR Prediction of Ames Mutagenicity.
Dr. Kiyohiro Hashimoto
Takeda Pharmaceutical, Japan

Biography
Kiyohiro Hashimoto, PhD, is an associate scientific fellow at Takeda Pharmaceutical Co. Ltd, serving
as a SME for genetic toxicology, safety assessment and qualification of impurity. He belongs to theJapanese Environmental Mutagen and Genome Society (JEMS), for which he is serving as BOD forinternational relationship matters. He also belongs to the Japanese Pharmaceutical Manufacturing
Association, leading the task force team as an expert of ICHM7 EWG member. He has been involvedin this genetic toxicology research area more than 20 years, and during this period he has stayed at University of North Carolina Chapel hill as a visiting scholar, supervised by Prof. Jim Swenberg. Main areaof research included biology of genotoxicity testing for drug discovery, mechanism investigation of
genotoxic compounds, and regulatory science related toxicology research.

Abstract
QSAR has shown remarkable progress since the beginning of the 21st century. In particular, it has been
widely used in industry-government-academia research institutes as a prediction tool for Ames test, andits recognition has remarkably improved. The ICHM7 guideline enacted in 2014 is considered to havecaused this phenomenon. Following the establishment of the guideline, pharmaceutical companies
became obligated to use QSARs to predict mutagenicity of impurities in pharmaceutical products, andbased on the results, they were required to submit the control of impurities to the regulatory authorities.
Therefore, authorities were also required to use QSAR, and the number of users spread drastically. In
addition, the prediction accuracy has been improving as the number of users increases. This is likely due
to a positive cycle where QSAR vendors continued to make efforts to incorporate a wider range of data
and users provided data to improve accuracy. For example, over 10,000 compounds were provided in the
QSAR challenge program and captured in the database, resulting in improved prediction accuracy. To
provide the speakers’ personal opinions on how the QSAR prediction accuracy will be improved, what
factors have hindered the improvement in accuracy, and whether the “QSAR prediction” will be accepted as an alternative to the existing Ames test in the future.

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S2-2
A Toxicity Pathway-Based Approach to Develop Adverse Outcome Pathway.
Prof. Dianke Yu
Qingdao University, China

Biography
Dianke Yu, Professor, School of Public Health, Qingdao University. Professor Yu received his Ph.D.
degree from Chinese Academy of Medical Science (CAMS), China. After working at National Center for
Toxicological Research (NCTR) for four years (2013-2017), he joined the school of public health in Qingdao University. He now serves as the Vice Dean of School of Public health since 2021. His main researchinterests are in molecular toxicology and systems toxicology, especially in the identification, epigenetic
modulation, and quantitative analysis of key toxicity pathways in response to environmental chemicals.
His research is supported by multiple fundings received from the National Key Research and Development Program of China, National Natural Science Foundation of China, and Thousand Young Talents
Recruitment Programe. He has published 120+ articles in well-respected SCI journals, including Nat
Genet, Environ Int, J Hazard Mater, Arch Toxicol, and Environ Pollut.

Abstract
With numerous new chemicals introduced into the environment every day, identification of their potential
hazards to the environment and human health is a considerable challenge. Toxicity pathway is an essentially physiological pathway that could function and maintain homeostasis, and once sufficiently perturbed tothe degree beyond adaptation, become toxicity pathway. Adverse outcome pathway (AOP), which sequentially starts from a molecular initiating event, triggers multiple key events in cells or organs, and eventually
results in an adverse outcome, is a promising tool to help achieve this goal as it can bring in vitro testing
into toxicity measurement and understanding. Here, we proposed a new approach to construct AOP based
on toxicity pathways, by integrating the omics data and systems biology understanding, which supplies
new clues to the identification of potential hazards and risk assessment of environmental chemicals.

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S2-3
Development of Physiologically Based Pharmacokinetic (PBPK) Models
Within Bayesian Framework for Perfluorooctane Sulfonate (PFOS) and Its
Implications in the Derivation of Health-Based Toxicity Values.
Research Assistant Prof. Wei-Chun Chou
University of Florida, United States

Biography
Dr. Wei-Chun Chou graduated from the Department of Biomedical Engineering and Environmental
Sciences at National Tsing Hua University and is currently working as a research assistant professor at the
Department of Environmental and Global Health and the Center for Environmental and Human Toxicology at the University of Florida. Dr. Chou’s research is to develop a computational model based on Bioinformatics, Computational toxicology, and artificial intelligence to study the research questions about environmental health and human health risk assessment. In 2019, he was awarded the Anderson & Clewell
Trainee Award and the Outstanding Postdoctoral Research Award from the Society of Toxicology (SOT).
His paper also was awarded the best paper award by the Biological Modeling and risk assessment Specialty Section of the SOT in 2020 and 2022. Dr. Chou participated in several NIH and USDA projects, including (1) NIH/NIBB R03 Grant: Physiologically based pharmacokinetic modeling and analysis of administration route-dependent tissue distribution of gold nanoparticles; (2) USDA/NIFA Award: Food Animal
Residue Avoidance Databank (FARAD); (3) NIH/NIBB R01 Grant: Development of a web-based predictive model of nanoparticle delivery to tumors by integrating physiologically-based pharmacokinetic modeling with artificial intelligence. He is currently a guest editor of Toxics and an invited reviewer for several
well-known international journals, such as Computation Toxicology, Environmental Health Perspectives,
Journal of Hazardous and Materials, and Environment International.

Abstract
Inter- and intra-species variability in chemical pharmacokinetics and toxicological endpoints results in asignificant difference in the estimation of reference dose (RfD), thus leading to an enormous challenge inhuman health risk assessments. Therefore, it is important to address an integrated framework with new
approach methods (NAMs) to characterize variability and susceptibility. Recently, we developed an
integrated framework by combing Bayesian statics with physiologically based pharmacokinetic (PBPK)"$&.$&.4
models to characterize uncertainty and variability between species, individuals, and life stages. This
Bayesian population PBPK model has been used in the estimation of RfD from interspecies extrapolations,
simulation of the internal dose metrics for potentially sensitive subpopulations, and prediction of in vitro
to in vivo extrapolation (IVIVE) of kinetic and toxicity data. In this presentation, I will introduce how wedevelop mechanistic PBPK model structure in different species, chemicals, and life stages within theBayesian hierarchical framework and application for a case study with Perfluorooctane Sulfonate (PFOS)
risk assessments.

S2-4
Analytical Development for Environmental Exposome Research.
Prof. Da Chen
Jinan University, China

Biography
Prof. Da Chen is a Professor and Associate Dean at the School of Environment, Jinan University. He
received his Ph.D. at The College of William and Mary in 2009 and doctoral training at the National Wildlife Research Centre, Environmental and Climate Change Canada. He had worked as an Assistant Professor at the Southern Illinois University Carbondale. Chen’s research has focused on the development of
exposome-based analytical platform, exploration of the environmental distributions and fate of chemicals
of emerging concern (CECs), and characterization of human exposure to CECs and subsequent healthrisks. In particular, his research focuses on gestational exposure to CECs and aims to study the links
between environmental exposure and adverse pregnancy outcomes from an exposome perspective. He has
published more than 150 scientific papers and received awards such as National Environmental Protection
Technology Award and Guangdong Science and Technology Award. Prof. Chen is currently an Associate
Editor of Environment International and Environmental Pollution, and an editorial board member of Environmental Science & Technology Letters. He is also a committee member of Environmental Science Society of China and Chinese Environmental Mutagen Society.

"$&.$&.4

Abstract
Over the past decade, “exposome” has emerged as a novel research paradigm in many fields including
epidemiology, biotechnology, clinical research, and other environmental health sciences. The concept of“human exposome” encompasses the totality of a person’s environmental exposures from conception
onwards, which complements the genome. The concept has driven the integration of both internal andexternal factors into the study of adverse health outcomes in humans in order to achieve a comprehensive
assessment of the causes and mechanisms associated with health outcomes. However, although the exposome concept is fascinating, the approach to “exposome” is very complicated and challenging. One of the
major challenges is to determine numerous exogenous and endogenous molecules in biological specimens
in order to characterize both external and internal chemical exposure. The numerous environmental chemicals complicate analytical characterization in human blood or urine. Complex environmental and biological transformation also make the identification of exposure biomarkers extremely difficult. Exposure
markers also dynamically change along with age, gender, population, and territories, requiring accuratemonitoring. In response to the analytical challenges during exposome applications, we developed an
integrated analytical platform to determine both exogenous and endogenous molecules in biological specimens. The framework combines target, suspect screening, and non-target techniques based advanced mass
spectrometry and databases. Target analysis can achieve high-throughput determination of over 600 environmental chemicals in blood and urine with small volumes. Suspect screening aims to determine chemicals structurally similar to known molecules and enhance the detection sensitivities via sample treatment
and mass spectral optimization. Non-target screening aims to capture mass spectral signals in order toscreen for possible chemicals in the samples with high-resolution mass spectrometer. The combined framework is expected to largely facilitate the application of exposome science in human health research.

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S2-5
Metabolic Mechanisms and Toxic Effects of Polycyclic Aromatic Hydrocarbons Regulated by CYP Enzymes Under Combined Pollution.
Associate Prof. Kai Luo
Southeast University, China

Biography
Dr. Kai Luo is now an associate professor in Key Laboratory of Environmental Medicine Engineering,
Ministry of Education, School of Public Health, Southeast University. Dr. Luo obtained his doctorate inGeography (Environmental Geography) from Peking University and then worked as a postdoctoral associate at Masonic Cancer Center, the University of Minnesota. Dr. Luo’s laboratory is focused on understanding the ways carcinogens in tobacco and the environment cause cancer. To do this he and his group study
the mechanisms by which these compounds enter the human body, are metabolized, and ultimately bind to
DNA, causing mutations that result in cancer. Dr Luo’s research team has developed methods to analyze
human urine for these compounds, their metabolites and the DNA damage caused by the carcinogens.

Abstract%HQ]R>D@S\UHQH %D3 LVDZHOOVWXGLHGSURFDUFLQRJHQWKDWLVPHWDEROLFDOO\DFWLYDWHGE\F\WRFKURPH3
enzymes. Cytochrome P450 especially CYP1 has been considered to play a central role in the metabolismof BaP, which is essential for the formation of DNA adducts or the detoxification metabolism. While previous studies got diverse results on the effect of induction of CYP1 on BaP-DNA adduct formation. We gave
RUDOGRVHVRIGHXWHUDWHGSKHQDQWKUHQH >'10]Phe), a non-carcinogenic surrogate of carcinogenic PAH such
DVEHQ]R>D@S\UHQHWRVPRNHUV 1 RUȝJGRVHV DQGQRQVPRNHUV 1 ȝJGRVH %LRDFWLYDWLRQSURGXFWV GLK\GURGLRODQGWHWUDRO DQGGHWR[LILFDWLRQSURGXFWV SKHQROV RI>'10]Phe were determinedin 6-h urine to obtain a comprehensive metabolic profile. Cigarette smoking increased the bioactivation of>'10]Phe and decreased its detoxification resulting in significantly different metabolic patterns between
smokers and non-smokers (P < 0.01), consistent with increased cancer risk in smokers. The Phe bioactivaWLRQUDWLRV >'10@3KH7WRWDO>'9]OHPhe) were significantly higher (2.3 (P < 0.01) to 4.8 (P < 0.001) fold) insmokers than non-smokers. With solid human in vivo evidence, our results for the first time demonstratethat induction of CYP1 enzymes by cigarette smoking enhances the metabolic activation of Phe, structurally representative of carcinogenic PAH BaP, in humans, strongly supporting their causal role in cancers
caused by smoking.
"$&.$&.4

S2-6
Applying Multi-Omics Approach to Reveal the Lung Cancer Biomarker.
Associate Prof. Ting Xiao
Chinese Academy of Medical Sciences and Peking Union Medical College, China

Biography
Ting Xiao graduated from Peking Union Medical College in 2005 with a doctor's degree in Oncology.
Since 2005, as an associate researcher, and a master's supervisor she has worked in the State Key Laboratory of molecular oncology, the Cancer Hospital of the Chinese Academy of Medical Sciences. The research
direction is the molecular mechanism and molecular markers of the occurrence and development of malignant tumors. By using multi omics, and the molecular markers for early diagnosis, efficacy evaluation andprognosis judgment of tumors are explored to develop their clinical application value. Has successively
presided over the National Natural Science Foundation of China, the Beijing Natural Science Foundationand other projects, and participated in the 973 program, the 863 program, the national key R & D program.

Abstract
Objective: In China, the incidence rate and mortality of lung cancer have ranked first among all malignant
tumors. Lung adenocarcinoma is the most common pathological type in non-small cell lung cancer,
accounting for about 50% of the incidence rate of non-small cell lung cancer. Compared with other pathological subtypes of lung cancer, the proportion of non-smoking lung adenocarcinoma population is significantly higher, indicating the complexity of its pathogenesis. The purpose of this study is to identify differential proteins that are significantly related to the occurrence, development and prognosis of lung adenocarcinoma by integrating proteomics and phosphorylation proteomics based on large-scale clinical data,
and to search for tumor markers of lung adenocarcinoma.
Methods: a total of 103 primary tumor tissues of lung adenocarcinoma patients and paired adjacent normallung tissues were included in this study. Differential proteins and phosphorylated proteins in tumor tissues
compared with normal lung tissues adjacent to cancer were identified by mass spectrometry and phosphorylation mass spectrometry. They were verified in large-scale independent samples by Western blot and"$&.$&.4
enzyme-linked immunosorbent assay (ELISA), The molecular mechanism of tumor markers was further
studied by molecular biological methods.
Results: through in-depth analysis of protein expression profile and phosphorylation post-translational
modification profile, a total of 11119 gene end products and 22564 phosphorylation modification sites
were finally identified. At the same time, clinical information and genomic feature data were integrated
and analyzed, and a proteome based Panoramic Map of lung adenocarcinoma was constructed. The study
also systematically revealed the proteomic characteristics of people with good and poor prognosis of lungadenocarcinoma, and found that lung adenocarcinoma with good prognosis was closely related to molecular biological processes such as fatty acid metabolism and oxidative phosphorylation, while lung adenocarcinoma with poor prognosis was mainly related to tumor epithelial mesenchymal transformation. And
further revealed the protein molecular characteristics of TP53 and EGFR, the two major gene mutations oflung adenocarcinoma in China. The representative marker Hsp90 AB1 was confirmed by plasma samples
of independent populations, and it was found that its protein concentration was closely related to poor
prognosis. Knockdown of hsp90ab1 in lung cancer cell lines can affect the cycle and apoptosis of lungcancer cells by phosphorylating key proteins.
Conclusion: This study is the first time to systematically depict the molecular map of lung adenocarcinoma at the protein level, and to find the molecular features closely related to the prognosis of patients. This
work provides important clues for understanding the occurrence and development of lung adenocarcinoma
through multi omics integration analysis, and also lays a transformation foundation for the development ofprecision medicine and clinical treatment of lung adenocarcinoma in the future.

S2-7
Airborne PM2.5 Exposome and Cardiovascular Health: A Population-based Integrated Methodology Establishment and Application.
Prof. Tiantian Li
Chinese Center for Disease Control and Prevention, China

Biography
Dr. Tiantian Li is the director of the Department of Environmental Health Risk Assessment, National Institute of Environmental Health, China CDC. Her major research interests include air pollution, climate

"$&.$&.4
and health. Dr. Li has been the PI for more than 10 national, provincial or ministerial level scientificresearch projects. She has published more than 100 SCI papers as the first/corresponding author on Nature
ClimateChange, Lancet Public Health, Lancet Planetary Health, Science Advances, Circulation, JACC, EHP andetc. Dr. Li won National Special Support Program for National High-level Young Talents in 2014.

Abstract
The Global Burden of Disease (GBD) Study 2019 showed that there were nearly 4.14 million excess deaths
related to PM2.5 globally, of which 2.48 million were caused by cardiovascular disease. Previous toxicology
studies have confirmed the toxicity of PM2.5 components. However, epidemiological studies have only
found that common components in PM2.5 have cardiovascular effects. Recent studies have detected large
amounts of low-concentration organic components in PM2.5. These PM2.5 components have a wide range ofsources and are closely related to people's production and life, which can be called airborne PM2.5 exposome. The current study lacks the epidemiological integrated methodology of the population-based studyof the association of airborne PM2.5 exposome with cardiovascular health, so there is an urgent need toestablish a population-based integrated methodology to elucidate the effect of airborne PM2.5 exposome on
cardiovascular health and identify the key components. We established a systematic integrated methodology for airborne exposomes and cardiovascular indicators, and apply this integrated methodology to the
population, using QTc interval as an example, to elucidate the mixtures effect of airborne PM2.5 exposome,and to further identify key organic components. We detected 224 organic components in PM2.5, and thosewith detection rates greater than 80% were included in the statistical analysis. Mixtures effects from multiple organic components and independent effects from selected organic components on QTC interval wereidentified and validated. Among the eight key organic components (i.e., TCIPP, BHT-CHO, DnBA/DiBA,
BP3, IPP, UV-328 and TPIB) associated with QTC interval prolongation and adverse changes of cardiovascular biomarkers, TCIPP, DnBA/DiBA and BHT-CHO were finally screened out as potential exposure
markers for the population health effect. Our findings could provide the latest scientific evidence for the
cardiovascular health risks of exposure to airborne PM2.5 exposome and highlight the important contributions of organic components of PM2.5 to the risks of cardiovascular diseases.

"$&.$&.4

S2-8
Integrated-Studies Interpreted Oligophagous Butterfly Tolerate to Strong Mutagen Aristolochic Acids.
Prof. Yang Luan
Shanghai Jiao Tong University, China

Biography
Dr. Yang Luan received her Ph.D. in 2003 from the Shenyang Pharmaceutical University, worked as a postdoctoral fellow in the NIHS, Japan from 2003 to 2006. She began her scientific career in toxicology in2006 at Shanghai Institute of Material Medical, joined Shanghai Jiaotong University in 2013. Dr. Luan’s
research program is focused on utilizing appropriate in vivo and in vitro mutation assays and biological and-omics techniques to provide key toxicological information for exogenous chemicals, including environmental pollutants and herbal medicine, and developing potential biomarkers on genotoxicity, developing
new technology on whole genome-widely ultra-low frequencies mutation sequencing. She is the Regional
Editor of Mutation Research - Genetic Toxicology and Environmental Mutagenesis, and editorial memberof Mutagenesis, Genes &Environment. She participated in OECD genotoxicity guidelines developing as agroup member and has been involved the work of international genotoxicity testing expert working group(IWGT) .

Abstract
Herbal medicines containing aristolochic acids (AAs) have drawn great attention in recent years, due totheir carcinogenic potential. The carcinogenic effects of AAs are generally considered to result from their
metabolic activation to reactive intermediates, and the consequent formation of DNA adducts and induction of gene mutation. However, the underlying mechanisms of their bioactivation have not been fully
elucidated. In the present study, aristolochiaceae-feeding swallowtail butterflies P. aristolochiae was studied to investigate their AAs-toxicity tolerance mechanisms. P. polytes that feeds on non-toxic plants wasused as the control. Firstly, whole-genome de novo sequencing and assembly were conducted using
Oxford Nanopore Technologies, followed by Hi-C analysis and functional annotation of high-quality transcriptomes by Illumina sequencing. We then conducted ADME studies, after the treatment of aristolochic
acid I (AAI), AAI and its main metabolites in the body, feces, and osmeterial secretion of the larvae were

"$&.$&.4
quantitated by using LC-MS/MS. ADME results revealed sequester and biotransformation of AAI in P.
aristolochiae, but not in P. polytes. DNA adducts formation is believed as molecular initiating event of
AAs-induced carcinogenesis. DNA adducts results revealed the metabolic activation of AAI in P. aristolochiae, and the consequent dA-AAI/II and dG-AAI/II formation were observed in larvae, pupa and imago
but not in embryo stage, and the level increased during the entire life cycle, with the DNA adducts level inimagos was about 3 times higher of larvae. To better understand the molecular mechanisms, the transcriptome of larvae were sequenced before and after AAI treatment, and differentially expressed genes (DEGs)
were identified. KEGG pathway analysis showed that DEGs were enriched in the metabolic pathways, thebiosynthesis of secondary metabolites, and the DNA damage and repair. Candidate genes including
nitroreductase, organic cation transporters, and DNA repair genes were identified. Comparative genomic
analysis between the P. polytes and P. aristolochiae revealed mutation or deletion on some candidate
genes, suggesting the consequence of evolution for P. aristolochiae to tolerate the toxicity from AAs. To
reveal the mechanism underlying how P. aristolochiae repaired the AAs-induced DNA lesion and maintainits genome integrity for stable heredity, we sequenced the transcriptome of P. aristolochiae at embryo,larva, pupa and imago stage, moreover, we investigated the spatiotemporal dynamics of germ cells versus
somatic cells in the testis of adult P. aristolochiae. Our findings may provide basis for the underlying
molecular mechanisms of AAs toxicity in humans.

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Contacts us
ACEM/CEMS 2022 Secretariat Rui Zhang E-mail: ACEM-2022@cnems.org.cn
Website: Chinese Environment Mutagen Society http://www.cnems.org.cn/
Scientific Organization: Sun Yat-sen University
Rui Zhang, Email: ACEM-2022@cnems.org.cn zhangr93@mail2.sysu.edu.cn
Yuzhi Guo, Email: guoyzh25@mail2.sysu.edu.cn
Organizer: Qingdao University
Jinglong Tang, Email: tangjinglong@qdu.edu.cn
Chuanhai Li, Email: chli@qdu.edu.cn
Finance: Qingdao University
Yuan Jin, Email: yuanjin@qdu.edu.cn
Lin Lu, Email: lulin163@126.com
Exhibitions: Qingdao University
Yongfeng Lin, Email: VGOLQ\RQJIHQJ#FRP˩
Xiaoting Jin, Email: xtjin@qdu.edu.cn