Assessment of exposure and susceptibility to aromatic amine carcinogens.
As a consequence of human exposure to carcinogenic aromatic amines, biochemical approaches to risk assessment have emphasized metabolic determinants of individual susceptibility and quantification of arylamine-macromolecular adducts. A known genetic polymorphism in humans, hepatic arylamine acetyltransferase activity, has been associated with differences in individual susceptibility to urinary bladder (slow acetylators) and colorectal (rapid acetylators) cancers. Similarly, the high specificity of an inducible human cytochrome P450 towards the N-oxidation of 4-aminobiphenyl and other aromatic amines is consistent with metabolic differences that can be used to predict relative human risk. Exposure to aromatic amines has also been documented, primarily by quantification of adducts with protein or DNA. Using 32P-postlabelling methods and a competitive avidin/biotin-amplified enzyme-linked immunoassay, we have estimated 4-aminobiphenyl-DNA adduct levels in surgical samples of human peripheral lung and urinary bladder epithelium and report values ranging from 2 to 97 adducts per 10(8) nucleotides.
Kadlubar
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Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR.
Talaska
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Lang
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Benson
R W
RW
Roberts
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DW
D000107:Acetylation; D000588:Amines / Q000633:toxicity*; D000611:Aminobiphenyl Compounds / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000378:metabolism / Q000633:toxicity*; D015179:Colorectal Neoplasms / Q000209:etiology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004784:Environmental Monitoring / Q000379:methods*; D006801:Humans; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D000588:Amines; D000611:Aminobiphenyl Compounds; D002274:Carcinogens, Environmental; C006757:4-biphenylamine; D004247:DNA; D003577:Cytochrome P-450 Enzyme System