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Harvard School of Public Health

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Superfund Research Program

Arsenic Mode of Action in Cancer: Models of Epigenetic Mechanism

Project Leader: Karl T. Kelsey
Grant Number: P42ES005947
Funding Period: 2000 - 2006

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Project Summary (2000-2006)

Arsenic poses unique problems for environmental health scientists because it is recognized as a human carcinogen, but is not carcinogenic in animal models. Furthermore, arsenical compounds do not induce gene mutations, although they do potentiate the genotoxic effects of other mutagens and are associated with chromosomal abnormalities. These properties indicate that arsenic has a mode of action different from other well-characterized environmental carcinogens whose actions are mediated by DNA damage. One hypothesis is that arsenic acts through epigenetic mechanisms; arsenic may produce reversible cell alterations that influence the expression of genes involved in growth and differentiation. Researchers are investigating the effects of arsenic exposure in the context of an ongoing population based case control study of bladder cancer. The hypothesis is that DNA methylation of genes in the causal pathway for disease occurs with a higher frequency in cases with bladder cancer who are also exposed to high levels of arsenicals. Thus, project investigators are studying methylation and mutation of genes in the causal pathway for the genesis of bladder cancer, with special attention to any association with exposure to arsenic.

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