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, Keiji Kondo

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 (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
Volume559
Issue number1-2
DOIs
Publication statusPublished - Apr 11 2004

Fingerprint

Aberrant Crypt Foci
Mutagenesis
Amines
Colon
2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole
Antimutagenic Agents
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
Comet Assay
Carcinogenesis
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Anticarcinogenic Agents
Cytochrome P-450 CYP1A2
Inbred ICR Mouse
Micronucleus Tests
DNA Adducts
Inbred F344 Rats
Salmonella typhimurium
Cricetulus
Carcinogens
DNA Damage

Keywords

  • 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

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Inhibitory effects of beer on heterocyclic amine-induced mutagenesis and PhIP-induced aberrant crypt foci in rat colon. / Nozawa, Hajime; Tazumi, Kyoko; Sato, Kaoru; Yoshida, Aruto; Takata, Jun; Arimoto, Sakae; Kondo, Keiji.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 559, No. 1-2, 11.04.2004, p. 177-187.

Research output: Contribution to journalArticle

Nozawa, Hajime ; Tazumi, Kyoko ; Sato, Kaoru ; Yoshida, Aruto ; Takata, Jun ; Arimoto, Sakae ; Kondo, Keiji. / Inhibitory effects of beer on heterocyclic amine-induced mutagenesis and PhIP-induced aberrant crypt foci in rat colon. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2004 ; Vol. 559, No. 1-2. pp. 177-187.
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AU - Yoshida, Aruto

AU - Takata, Jun

AU - Arimoto, Sakae

AU - Kondo, Keiji

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N2 - 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.

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KW - 3-amino-1-methyl-5H- pyrido[4,3-b]indole

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KW - HCAs

KW - Heterocyclic amines

KW - IQ

KW - MeIQx

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