Arsenic Exposure through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India
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Title |
Arsenic Exposure through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India |
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Creator |
Chatterjee, Debmita
Bhattacharjee, Pritha Sau, Tanmoy Jyoti Das, Jayanta K Sarma, Nilendu Bandyopadhyay, Apurba K Roy, Sib Sankar Giri, Ashok K |
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Subject |
Cell Biology & Physiology
Molecular & Human Genetics |
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Description |
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 b-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 overexpression of ALT associated proteins TRF-1 and TRF-2 with higher increase in TRF-2. An increased risk for developing Asinduced skin lesions was found for individuals having RTL greater than 0.827 (odds ratio, 13.75; 95% CI: 5.66–33.41; P |
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Publisher |
John Wiley & Sons
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Date |
2015
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/2377/1/MOLECULAR_CARCINOGENESIS__Vol_54(__9)__800%2D809;2015.pdf
Chatterjee, Debmita and Bhattacharjee, Pritha and Sau, Tanmoy Jyoti and Das, Jayanta K and Sarma, Nilendu and Bandyopadhyay, Apurba K and Roy, Sib Sankar and Giri, Ashok K (2015) Arsenic Exposure through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India. Molecular Carcinogenesis, 54 (9). pp. 800-809. ISSN 0899-1987 |
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Relation |
http://dx.doi.org/10.1002/mc.22150
http://www.eprints.iicb.res.in/2377/ |
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