The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis.
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.
Nebert
Daniel W
DW
Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, Ohio 45267-0056, USA. dan.nebert@uc.edu
Dalton
Timothy P
TP
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001711:Biotransformation; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D010597:Pharmacogenetics; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D001189:Aryl Hydrocarbon Hydroxylases; D002274:Carcinogens, Environmental; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse