Inhibitory effects of beer on heterocyclic amine-induced mutagenesis and PhIP-induced aberrant crypt foci in rat colon

Hajime Nozawa, Kyoko Tazumi, Kaoru Sato, Aruto Yoshida, Jun Takata, Sakae Arimoto-Kobayashi, Keiji Kondo

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28 Citations (Scopus)


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 (13mg/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 (75mg/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.

Original languageEnglish
Pages (from-to)177-187
Number of pages11
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Issue number1-2
Publication statusPublished - Apr 11 2004


  • 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
  • 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline
  • 2-amino-3-methylimidazo[4,5-f]-quinoline
  • 3-amino-1-methyl-5H- pyrido[4,3-b]indole
  • Glu-P-1
  • HCAs
  • Heterocyclic amines
  • IQ
  • MeIQx
  • PhIP
  • Trp-P-2

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis


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