title: Inhibitory effects of beer on heterocyclic amine-induced mutagenesis and PhIP-induced aberrant crypt foci in rat colon.
abstract: Anti-mutagenic and anti-carcinogenic effects of beer on heterocyclic amine (HCA)-induced carcinogenesis were studied in vitro and in vivo. Four commercial beers (two pilsner-type, black, and stout) showed inhibitory effects against five HCAs, 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), in the Ames assay using Salmonella typhimurium TA98 in the presence of rat S9 mix. The inhibitory effects of dark-colored beers (stout and black beer) were greater than those of pilsner-type beers. Dark-colored beers suppressed CYP1A2 activity in a dose-dependent manner, suggesting that inhibition of HCA activation is partly responsible for their strong anti-mutagenic effects. Anti-mutagenic effects were also observed when the pooled human S9 mix or activated IQ was used in the assay. The micronucleus test using Chinese hamster lung CHL/IU cells showed that the addition of freeze-dried samples of pilsner-type and stout beer to the culture medium significantly reduced the number of cells with micronuclei induced with PhIP or Trp-P-2. Single-cell gel electrophoresis assay (comet assay) revealed that oral ingestion of pilsner-type and stout beers for 1 week significantly inhibited DNA damage in the liver cells of male ICR mice exposed to MeIQx (13 mg/kg, i.p.). A decrease in the formation of DNA adducts was also observed using a 32P-postlabeling method. Male Fischer 344 rats orally received PhIP (75 mg/kg, five times a week for 2 weeks) and aberrant crypt foci (ACF) formation in the colon was analyzed after 5 weeks. The number of ACF was significantly reduced in rats fed a diet containing freeze-dried beer. These results suggest that beer inhibits the genotoxic effects of HCAs and may reduce the risk of carcinogenesis caused by food borne carcinogens.
authors.affiliation: Central Laboratories for Key Technology, Kirin Brewery Co. Ltd., 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. h-nozawa@kirin.co.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Nozawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tazumi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sato
authors.forename: Aruto
authors.initials: A
authors.lastname: Yoshida
authors.forename: Jun
authors.initials: J
authors.lastname: Takata
authors.forename: Sakae
authors.initials: S
authors.lastname: Arimoto-Kobayashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Kondo
mesh_terms: D000588:Amines / Q000037:antagonists & inhibitors*; D000818:Animals; D016587:Antimutagenic Agents / Q000032:analysis / Q000494:pharmacology*; D001515:Beer / Q000032:analysis*; D002478:Cells, Cultured; D003106:Colon / Q000473:pathology; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000037:antagonists & inhibitors*; D008099:Liver / Q000737:chemistry; D015162:Micronucleus Tests; D016296:Mutagenesis / Q000187:drug effects*; D010088:Oxidoreductases / Q000032:analysis; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013050:Spectrometry, Fluorescence
chemical_list: D000588:Amines; D016587:Antimutagenic Agents; D018736:DNA Adducts; D006571:Heterocyclic Compounds; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019388:Cytochrome P-450 CYP1A2