Review
Nature Reviews Cancer 6, 947-960 (December 2006) | doi:10.1038/nrc2015
The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis
Daniel W. Nebert1 & Timothy P. Dalton1 About the authors
Abstract
Some cytochrome P450 (CYP) heme-thiolate enzymes participate in the detoxication and, paradoxically, the formation of reactive intermediates of thousands of chemicals that can damage DNA, as well as lipids and proteins. CYP expression can also affect the production of molecules derived from arachidonic acid, and alters various downstream signal-transduction pathways. Such changes can be precursors to malignancy. Recent studies in mice have changed our perceptions about the function of CYP1 enzymes. We suggest a two-tiered system to predict an overall inter-individual risk of tumorigenesis based on DNA variants in certain 'early defence' CYP genes, combined with polymorphisms in various downstream target genes.
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Author affiliations
- Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, Ohio 45267-0056, USA.
Correspondence to: Daniel W. Nebert1 Email: dan.nebert@uc.edu
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