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Proposed mechanisms for arsenic carcinogenicity: implications for the shape of the dose-response curve.
Toxicologist 2003 Mar; 72(S-1):112-113
Epidemiological studies have established that inorganic arsenic is a significant human carcinogen that causes tumors predominantly in the skin and bladder following oral exposure and in the lung following inhalation. Despite numerous experimental studies and proposed hypotheses, there is no consensus on arsenic's mechanism of action. It does not behave as most classical chemical carcinogens, including other metals such as cadmium or chromium. In this respect, it does not induce bacterial or mammalian cell mutations at relevant concentrations nor does it produce tumors in standard one- or two-stage animal bioassays. Recent advances have allowed development of atypical rat or mouse models for arsenic carcinogenesis. These, in conjunction with in vitro studies, have suggested that arsenic may be inducing carcinogenesis by one or more mechanisms including it's ability to cause global hypomethylation leading to heritable changes in gene expression, act as a 'comutagen' by inhibiting DNA repair, to induce chronic growth signaling through persistent activation of the MAPKinase pathway and induce oxidative damage through formation of dimethylarsenic radicals. Such mechanisms suggest the likelihood that the dose-response for arsenic may be non-linear in the low dose region and evoke the possibility that such events as genomic instability and by-stander effects may be involved.
Arsenic-compounds; Carcinogenicity; Epidemiology; Exposure-levels; Tumors; Lung-disorders; Cadmium-compounds; Cadmium-dust; Chromium-compounds; Models; Animal-studies; Animals; Laboratory-animals; In-vitro-studies
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah
WV; Geneva, Switzerland
Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division