Inhibitory effects of beer on mutation in the Ames test and DNA adduct formation in mouse organs induced by 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
An evaluation of the antigenotoxic potential of beer components against carcinogens contained in the human diet, namely heterocyclic amines (HCAs) including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was determined. The protective mechanism involved was also investigated. Beer samples were found to inhibit the mutagenicity of HCAs in the Ames test. Beer solution, consisting of a freeze-dried and dissolved sample, given as drink-water significantly reduced the formation of PhIP-DNA adducts in mouse colon and lung compared to control mice fed with PhIP in the absence of beer solution. Furthermore, beer solution added in the diet as a food additive mimic significantly reduced the amount of DNA adducts present in the liver and lung of mice fed with PhIP. In an effort to investigate the mechanism responsible for the observed protective effect, the effect of beer solutions on HCA metabolizing enzymes was investigated. Beer solutions inhibited the activity of CYP1A1 and CYP1A2, as determined from deethylation and demethylation assays using 7-ethoxy- and 7-methoxyresolufin, respectively. Considering the overall suppression of PhIP genotoxicity by beer, this study confirmed that beer components can interfere with the enzyme activity involved in the metabolism of HCAs and subsequently suppress the observed genotoxicity. The results of this study showed that beer components act in a protective capacity against the genotoxic effects of heterocyclic amines in vivo.
Arimoto-Kobayashi
Sakae
S
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Sciences, Okayama University, Japan. arimoto@cc.okayama-u.ac.jp
Ishida
Rie
R
Nakai
Yumi
Y
Idei
Chiho
C
Takata
Jun
J
Takahashi
Eizo
E
Okamoto
Keinosuke
K
Negishi
Tomoe
T
Konuma
Toshimitsu
T
D000588:Amines / Q000633:toxicity; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001515:Beer; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects* / Q000378:metabolism*; D004032:Diet; D006571:Heterocyclic Compounds / Q000633:toxicity; D007093:Imidazoles / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D010088:Oxidoreductases / Q000378:metabolism
D000588:Amines; D016587:Antimutagenic Agents; D018736:DNA Adducts; D006571:Heterocyclic Compounds; D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2