title: Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, 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 < 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.
authors.affiliation: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Debmita
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Environmental Science, University of Calcutta, Kolkata, India.
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhattacharjee
authors.affiliation: Sir Nil Ratan Sircar Medical College and Hospital, Kolkata, India.
authors.forename: Tanmoy J
authors.initials: TJ
authors.lastname: Sau
authors.affiliation: Department of Dermatology, West Bank Hospital, Howrah, West Bengal, India.
authors.forename: Jayanta K
authors.initials: JK
authors.lastname: Das
authors.affiliation: Sir Nil Ratan Sircar Medical College and Hospital, Kolkata, India.
authors.forename: Nilendu
authors.initials: N
authors.lastname: Sarma
authors.affiliation: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Apurba K
authors.initials: AK
authors.lastname: Bandyopadhyay
authors.affiliation: Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Sib Sankar
authors.initials: SS
authors.lastname: Roy
authors.affiliation: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Giri
mesh_terms: D000328:Adult; D000375:Aging / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity*; D063646:Carcinogenesis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D060766:Drinking Water / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D060766:Drinking Water; D016159:Tumor Suppressor Protein p53; D014874:Water Pollutants, Chemical; D019098:Telomerase; D001151:Arsenic
keywords: alternative lengthening; arsenic; humans; senescence; telomere