title: The role of AHR-inducible cytochrome P450s in metabolism of polyunsaturated fatty acids.
abstract: The environmental pollutant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) is the prototype of a large number of non-genotoxic carcinogens, dietary phytochemicals and endogenous metabolites that act via binding the aryl hydrocarbon receptor (AHR). The TCDD-liganded AHR massively upregulates CYP1A1, CYP1A2 and CYP1B1 in many mammalian organs. We demonstrated that TCDD treatment markedly increases the levels of several epoxides and diol metabolites of the epoxides of both ω-6 and ω-3 polyunsaturated fatty acids (PUFA) in the liver and lungs of mice, in an aryl hydrocarbon receptor-dependent fashion, and most likely via the activities of the CYP1 family members. ω-6 Epoxides are known to stimulate tumor growth, angiogenesis, and metastasis in mice. Interestingly, ω-3 epoxides have the opposite effect on these parameters. TCDD and other AHR agonists may, therefore, impact angiogenesis, growth and metastasis of tumors in either a positive or negative way, depending on the relative levels of ω -6 epoxides and ω-3 epoxides generated in the host and/or tumor cells. This is of potential relevance to carcinogenesis by AHR agonists in the human, since the human population is exposed to widely varying ω-6: ω-3 PUFA ratios in the diet.
authors.affiliation: a UCLA, Pathology, CHS, UCLA , Los Angeles , CA , USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hankinson
mesh_terms: D000818:Animals; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D005231:Fatty Acids, Unsaturated; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System
keywords: 2,3,7,8-Tetrachlorodibenzo-ρ-dioxin (TCDD); CYP1; aryl hydrocarbon receptor (AHR); eicosanoid; metastasis; omega-3 (ω-3) PUFA; omega-6 (ω-6) PUFA; oxylipin; polyunsaturated fatty acids (PUFA); tumor growth