Abstract 6584: Potential carcinogenic effects of electronic nicotine delivery systems through epigenetic reprogramming in oral, brain, and lung stem cells
Authors: Shepard Akilah , Yearde Oneilia , Sanchez Juan , Amador Ryan , Xirinachs Gabriel , Hernandez Erika , Corrales Elizabeth , Das Swarnava , Ruiz Marco , Das Madhumita , Stiffin Rose M. , Sherman Marilyn , Manzon Alessandra , Huisso Ayivi , Das Jayanta K. 
Published: April 2023

Abstract
Recent scientific studies exhibited that the electronic nicotine delivery systems (ENDS) aerosols comprise numerous carcinogens namely propylene glycol, diacetyl, formaldehyde, acetaldehyde, crotonaldehyde (2-butenal), acetone, acetyl propionyl (2,3-pentanedione), acrolein, nicotine, arsenic, cadmium and radioisotopes, such as Polonium-210 and lead-210. However, there was no such investigation for clarifying the mechanism of carcinogenic effects and epigenetic reprogramming of human oral, brain, and lung stem cells. In this study, we investigated the carcinogenic effects of ENDS aerosols, and the mechanism of epigenetic reprogramming using the Comparative Toxico-genomics Database (CTD), NIH Toxicology Data Network (TOXNET), the database of the National Institute of Environmental Health Sciences (NIEHS), AACR Genomics Evidence Neoplasia Information Exchange (GENIE) database, and other bioinformatics databases. We found from CTD analysis that the chemical gene interactions showed approximately 3% of genes highly expressed by propylene glycol and diacetyl from a total of 98 genes. The AACR GENIE database analysis showed EGFR, is associated with gliomas (191 clinical data, DFCI glioma cohort), found among 98 genes regulated by propylene glycol and diacetyl. The CTD analysis also exhibited the chemical gene interactions of highly expressed 9 common genes (with miR140 by propylene glycol, and formaldehyde from a total of 3983 genes; 5 common genes by propylene glycol, acetaldehyde, from a total of 275 genes; 1 common gene by propylene glycol, crotonaldehyde (2-butenal), from a total of 227 genes; 7 common genes by propylene glycol, acrolein from total 2185 genes; 18 common genes by propylene glycol, and nicotine from total 1244 genes; 11 common genes by propylene glycol, and arsenic from total 4983 genes; 9 common genes with HDAC4, CD86, miR21 by propylene glycol, and cadmium from total 5242 genes. The ENDs aerosols contain Polonium-210 and lead-210 (concentration; 13 ± 2 Bq/kg), which have been reported as Group 1 human carcinogens and emit alpha particles. We found that alpha particles caused DNA lesions, and gene mutations in human oral, brain, and lung stem cells and resulted in long-term chromosomal instability in primary human T lymphocytes by analyzing recent works of literature. The epigenetic mechanisms of histone modifications and these potential carcinogens have been revealed by the database of NIH Roadmap Epigenomics Mapping Consortium and our analysis discovered that Mitogen-activated protein kinase 1(MAPK1) is epigenetically reprogrammed with close interaction of teen genes. Therefore, it is important to find the actual epigenetic mechanism of transcriptional regulation by these potential carcinogens on oral, lung, and brain stem cells, and our current study revealed this important relationship.
Citation Format: Akilah Shepard, Oneilia Yearde, Juan Sanchez, Ryan Amador, Gabriel Xirinachs, Erika Hernandez, Elizabeth Corrales, Swarnava Das, Marco Ruiz, Madhumita Das, Rose M. Stiffin, Marilyn Sherman, Alessandra Manzon, Ayivi Huisso, Jayanta K. Das. Potential carcinogenic effects of electronic nicotine delivery systems through epigenetic reprogramming in oral, brain, and lung stem cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6584.