title: Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.
abstract: The food-derived heterocyclic amines (HCAs) 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), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins. Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt MF. Vitamin E was the most effective at decreasing Hprt MF. In addition, we determined whether carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone. Although the mechanisms of action of the antioxidants remain to be determined, the results indicate that dietary-derived HCA treatment induced MF in rat lymphocytes and suggest that antioxidants in food or taken as supplements could, in part, counteract such mutagenic activities.
authors.affiliation: Division of Genetic and Reproductive Toxicology, Division of Biometry and Risk Assessment, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Montgomery
authors.forename: Jessica
authors.initials: J
authors.lastname: Murphy
authors.forename: James J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Varsha G
authors.initials: VG
authors.lastname: Desai
authors.forename: Lynda
authors.initials: L
authors.lastname: McGarrity
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Morris
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Casciano
authors.forename: Anane
authors.initials: A
authors.lastname: Aidoo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005502:Food; D005979:Glutathione Peroxidase / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D014815:Vitamins; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase