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Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1.
- Source :
-
Cancer science [Cancer Sci] 2004 Jan; Vol. 95 (1), pp. 1-6. - Publication Year :
- 2004
-
Abstract
- Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed environmental chemicals. PAHs acquire carcinogenicity only after they have been activated by xenobiotic-metabolizing enzymes to highly reactive metabolites capable of attacking cellular DNA. Cytochrome P450 (CYP) enzymes are central to the metabolic activation of these PAHs to epoxide intermediates, which are converted with the aid of epoxide hydrolase to the ultimate carcinogens, diol-epoxides. Historically, CYP1A1 was believed to be the only enzyme that catalyzes activation of these procarcinogenic PAHs. However, recent studies have established that CYP1B1, a newly identified member of the CYP1 family, plays a very important role in the metabolic activation of PAHs. In CYP1B1 gene-knockout mice treated with 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene, decreased rates of tumor formation were observed, when compared to wild-type mice. Significantly, gene expression of CYP1A1 and 1B1 is induced by PAHs and polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin through the arylhydrocarbon receptor. Differences in the susceptibility of individuals to the adverse action of PAHs may, in part, be due to differences in the levels of expression of CYP1A1 and 1B1 and to genetic variations in the CYP1A1 and 1B1 genes.
- Subjects :
- Animals
Aryl Hydrocarbon Hydroxylases genetics
Biotransformation
Cytochrome P-450 CYP1A1 genetics
Cytochrome P-450 CYP1B1
Genetic Predisposition to Disease
Humans
Aryl Hydrocarbon Hydroxylases metabolism
Carcinogens, Environmental metabolism
Cytochrome P-450 CYP1A1 metabolism
Polycyclic Aromatic Hydrocarbons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1347-9032
- Volume :
- 95
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 14720319
- Full Text :
- https://doi.org/10.1111/j.1349-7006.2004.tb03162.x