DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and carcinogenesis

被引:300
作者
Schut, HAJ
Snyderwine, EG
机构
[1] NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA
[2] Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA
关键词
D O I
10.1093/carcin/20.3.353
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds produced during the pyrolysis of creatine, amino acids and proteins. The major subclass of HCAs found in the human diet comprise the amino-imidazoazaarenes (AIAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All, except DiMeIQx, have been shown to be carcinogenic in animals. These compounds are present in cooked muscle meats at the p.p.b. level. Since the discovery of the HCAs in the late 1970s, many studies have examined the DNA adducts of these compounds. This review compiles the literature on AIA-DNA adducts including their identification and characterization, pathways of formation, mutagenesis in vitro and in vivo, and their association with carcinogenesis in animal models. It is now known that metabolic activation leading to the formation of DNA adducts is critical for mutagenicity and carcinogenicity of these compounds. All of the AIAs studied adduct to the guanine base, the major adduct being formed at the C8 position, Two AIAs, IQ and MeIQx, also form minor adducts at the NZ position of guanine, A growing body of literature has reported on the mutation spectra induced by AIA-guanine adducts, Studies of animal tumors induced by AIAs have begun to relate AIA-DNA adduct-induced mutagenic events with the mutations found in critical genes associated with oncogenesis. Several studies have demonstrated the feasibility of chemoprevention of AIA tumorigenesis, Only a few studies have reported on the detection of AZA-DNA adducts in human tissues; difficulties persist in the routine detection of ALA-DNA adducts in humans for the purpose of biomonitoring of exposure to AIAs, The AIAs are nevertheless regarded as possible human carcinogens, and future research on AIA-DNA adducts is likely to help address the role of AIAs in human cancer.
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页码:353 / 368
页数:16
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