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Proposed mechanisms for arsenic carcinogenicity: implications for the shape of the dose-response curve.

Authors
Luster-M
Source
Toxicologist 2003 Mar; 72(S-1):112-113
NIOSHTIC No.
20022665
Abstract
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.
Keywords
Arsenic-compounds; Carcinogenicity; Epidemiology; Exposure-levels; Tumors; Lung-disorders; Cadmium-compounds; Cadmium-dust; Chromium-compounds; Models; Animal-studies; Animals; Laboratory-animals; In-vitro-studies
CAS No.
7440-43-9; 7440-47-3
Publication Date
20030301
Document Type
Abstract
Fiscal Year
2003
NTIS Accession No.
NTIS Price
ISSN
1096-6080
NIOSH Division
HELD
Source Name
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah
State
WV; Geneva, Switzerland
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