Long-term exposure to hexavalent chromium inhibits expression of tumor suppressor genes in cultured cells and in mice.

Autor: Fan Y; Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati, College of Medicine, 3223 Eden Ave., Cincinnati, OH 45267, USA., Ovesen JL, Puga A
Jazyk: angličtina
Zdroj: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) [J Trace Elem Med Biol] 2012 Jun; Vol. 26 (2-3), pp. 188-91. Date of Electronic Publication: 2012 May 19.
DOI: 10.1016/j.jtemb.2012.04.009
Abstrakt: We have used mouse hepatoma cells in culture to study acute, short-term high-dose effects of hexavalent chromium on gene regulation directed by the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP). We find that the mixture engages three major signaling pathways: (i) activation of detoxification genes; (ii) induction of signal transduction effectors; and (iii) epigenetic modification of chromatin marks. Preliminary results in mice exposed to mixtures of low doses of Cr(VI) plus BaP indicate that all three pathways are likely to be engaged also in long-term effects resulting from exposure to environmentally relevant doses of the mixture that inhibit the expression of tumor suppressor genes. Given the toxicity and carcinogenicity of these mixtures, we expect that a two-way analytical approach, from cells in culture to biological effects in vivo and vice versa, will provide a better understanding of the molecular mechanisms responsible for the biological effects of mixtures. By focusing both the in vivo and the in vitro work into long-term, low-dose, environmentally relevant exposures, we expect to develop much needed information pertinent to the type of diseases found in human populations exposed to mixtures of environmental toxicants.
(Copyright © 2012 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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