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Elevated Human telomerase reverse transcriptase gene expression in blood cells associated with chronic and arsenic exposure in Inner Mongolia, China
Citation:
Mo, J., Y. Xia, Z. Ning, T. J. WADE, AND J. S. MUMFORD. Elevated Human telomerase reverse transcriptase gene expression in blood cells associated with chronic and arsenic exposure in Inner Mongolia, China. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 117(3):354-360, (2009).
Impact/Purpose:
research results
Description:
BACKGROUND: Arsenic exposure is associated with human cancer. Telomerase containing the catalytic subunit, human telomerase reverse transcriptase (hTERT), can extend telomeres of chromosomes, delay senescence and promoting cell proliferation leading to tumorigenesis. OBJECTIVE: This study was to investigate arsenic effects on hTERT mRNA expression in humans and in vitro. METHOD: Water and toenail samples were collected and analyzed for arsenic from 324 Inner Mongolia residents exposed to arsenic via drinking water. Blood samples were quantified for hTERT mRNA expression using real-time PCR. The hTERT mRNA levels were linked to water and nail arsenic concentrations. Human epidermal keratinocytes were treated with arsenite to assess arsenic effects on hTERT expression in vitro. RESULTS: hTERT mRNA expression were significantly associated with arsenic concentrations of water (p<0.0001) and nail (p=0.002), adjusting age, sex, smoking and pesticide use. Females showed a higher slope than males (females’ slope=0.126, p=0.0005; males’ slope=0.079, p=0.017). In addition to water and nail arsenic concentrations, age (p<0.0001) and pesticide use (p=0.025) also showed significant association with hTERT expression. The hTERT expression levels decreased with age. Tobacco smoking did not affect hTERT expression (p=0.13). hTERT expression was significantly correlated with OGG1 and ERCC1 expression. The in vitro results also showed a dose-response relationship between arsenite concentrations and hTERT expression. Conclusions: hTERT expression was associated with arsenic exposure in vivo and in vitro. The increased hTERT expression may be a cellular response to genomic insults by arsenic and also implicate that arsenic may function as a tumor promoter in carcinogenesis in humans.
