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Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case‐control study in West Bengal, India

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. © 2014 Wiley Periodicals, Inc.