Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India
Authors: Tanmoy J Sau
Sib Sankar Roy
Jayanta K Das
Debmita Chatterjee
Apurba K Bandyopadhyay
Nilendu Sarma
Ashok K Giri
Pritha Bhattacharjee
Journal: Molecular Carcinogenesis (2015)
Discipline: CLINICAL MEDICINE
Keywords: alternative lengthening; arsenic; humans; senescence; telomere.
Affiliations: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Department of Environmental Science, University of Calcutta, Kolkata, India., Sir Nil Ratan Sircar Medical College and Hospital, Kolkata, India., Department of Dermatology, West Bank Hospital, Howrah, West Bengal, India., Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Abstract:  Arsenic (As) induces pre-malignant and malignant dermatological lesions, non-dermatological health effects and cancers in humans. Senescence involves telomere length changes and acquisition of senescence-associated secretory phenotype (SASP), which promotes carcinogenesis. Though in vitro studies have shown that As induces senescence, population based studies are lacking. We investigated the arsenic-induced senescence, telomere length alteration and its contribution towards development of As-induced skin cancer. The study participants included 60 each of As-exposed individuals with skin lesion (WSL), without skin lesions (WOSL) and 60 unexposed controls. Exposure assessment of drinking water and urine was done. SA β-gal activity, ELISA, and quantification of senescence proteins, alternative lengthening of telomere (ALT) associated proteins and telomerase activity were performed. Relative telomere length (RTL) was determined by qPCR. A significantly higher number of senescent cells, over-expression of p53 and p21 were observed in the As-exposed individuals when compared to unexposed. SASP markers, MMP-1/MMP-3 were significantly higher in the WSL but not IL-6/IL-8. A significant increase of RTL was observed in the WSL group, which was telomerase-independent but exhibited an over-expression of ALT associated proteins TRF-1 and TRF-2 with higher increase in TRF-2. An increased risk for developing As-induced skin lesions was found for individuals having RTL greater than 0.827 (odds ratio, 13.75; 95% CI: 5.66-33.41; P &lt; 0.0001). Arsenic induces senescence in vivo, but the SASP markers are not strictly over-expressed in the As-induced skin lesion group, whereas telomerase-independent elongation of telomere length might be useful for predicting the risk of development of As-induced skin lesions. 

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PubPeer comments:
 In this manuscript by Debmita Chatterjee et al., the figure 1a and 1b are the same image. The fig 1b is the 90 degree rotated version of the fig 1a. Also the images are a bit differently cropped. For better understanding marked with colored box circles. Original image as in the publication ![file] 90 degree rotated for easier understanding ![file] , 
 Dear Pubpeer team, Thank you for your queries. However, I cannot comment on those queries as I am a collaborating author and donu2019t have data of the paper. The corresponding author and the first author will be able to comment on those. I have already forwarded the queries to the corresponding author so that he will respond to the queries soon. With best regards, Yours sincerely, Sib Sankar Roy ,