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.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Aryl Hydrocarbon Hydroxylases / metabolism
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Biotransformation
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Carcinogens, Environmental / pharmacokinetics
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Carcinogens, Environmental / toxicity*
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Cell Transformation, Neoplastic / drug effects
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cytochrome P-450 CYP1A1 / metabolism
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Cytochrome P-450 CYP1A2 / metabolism
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Cytochrome P-450 CYP1B1
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Enzymologic
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Humans
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Metabolic Networks and Pathways
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Mice
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Models, Biological
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Neoplasms / chemically induced
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Neoplasms / enzymology*
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Neoplasms / genetics
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Pharmacogenetics
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Receptors, Aryl Hydrocarbon / metabolism
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Receptors, Cytoplasmic and Nuclear / metabolism
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Risk Assessment
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Risk Factors
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Signal Transduction*
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Transcription Factors / metabolism
Substances
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Carcinogens, Environmental
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DNA-Binding Proteins
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Isoenzymes
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Receptors, Aryl Hydrocarbon
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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farnesoid X-activated receptor
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Cytochrome P-450 Enzyme System
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Aryl Hydrocarbon Hydroxylases
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CYP1B1 protein, human
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Cyp1b1 protein, mouse
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP1A2
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Cytochrome P-450 CYP1B1