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TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS
Citation:
MO, J., T. J. WADE, Y. XIA, AND J. S. MUMFORD. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS. Presented at Society of Toxicology 46th Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukaryotic chromosomes, delay senescence and enhance cell proliferation. Telomerase activation is shown to promote tumor growth and maintain genome instability and has been suggested as biomarker for assessing cancer risk. The aim of this study is to investigate arsenic effects on hTERT gene expression. Ba Men residents in Inner Mongolia are chronically exposed to arsenic via well water and showed associated health effects, including cancer. The 324 study subjects, including equal number of males and females, have been exposed to arsenic for more than 10 years. Most subjects (76%) have been exposed to arsenic at the concentration of 0.34 to 200 µg/L and the remaining subjects exposed up to 826 µg/L. Water and whole blood samples were collected from the study subjects. RNA was isolated from the blood samples and cDNA was synthesized using reverse transcriptase. hTERT mRNA was quantified using real-time PCR and were linked to arsenic concentrations in drinking water. The results showed that levels of hTERT expression were positively associated with the concentrations of arsenic concentrations in drinking water (p<0.0001) after adjusting for age, sex, smoking and pesticide exposure. Among these factors, only age showed significance in affecting hTERT expression. This study provided a linkage between chronic arsenic exposure and telomerase expression in this human population and provided some insight into the mechanisms of arsenic carcinogenesis. The expression of hTERT may potentially be as a useful biomarker for assessing health effects from chronic arsenic exposure. (This abstract does not necessarily reflect U.S. EPA policy.)