Inhibitory effects of heterocyclic amine-induced DNA adduct formation in mouse liver and lungs by beer.
An evaluation of the in vivo antigenotoxic potential of beer components on heterocyclic amines including 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 3-amino-1-methyl-5H-pyrido[4.3-b]indole (Trp-P-2) was determined with particular focus on the target organs of tumorigenesis, and the protective mechanisms involved were investigated. Beer-solution, consisting of a freeze-dried and dissolved sample, given as drinking water, reduced the formation of MeIQx-DNA adducts in mouse liver and lungs. Beer-solution added in the diet as a mimic of food additives also significantly reduced the amount of DNA adducts present in the liver, lung, and kidney DNA of mice fed with MeIQx compared to control mice fed with MeIQx in the absence of beer-solution. The amount of adducts present in the liver of mice with single or continuous administration of Trp-P-2 was significantly reduced when beer-solution was given as part of the diet compared to control mice given Trp-P-2 without beer-solution. Protective effects were observed both with lager- and stout-type samples. In an effort to investigate the mechanisms responsible for the observed protective effects, the effects of beer-solution on metabolizing enzymes for heterocyclic amines were examined. Beer-solutions inhibited the metabolic activation of Trp-P-2 to Trp-P-2(NHOH), as demonstrated by HPLC analysis. Considering the overall suppression of the genotoxicity of MeIQx and Trp-P-2 by beer, we have shown that beer components can inhibit the metabolic activation of heterocyclic amines and subsequently suppress the observed genotoxicity. The results of this study show that beer components are protective against the genotoxic effects of heterocyclic amines on target organs associated with tumorigenesis in vivo.
Arimoto-Kobayashi
Sakae
S
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. arimoto@cc.okayama-u.ac.jp
Takata
Jun
J
Nakandakari
Namiko
N
Fujioka
Rie
R
Okamoto
Keinosuke
K
Konuma
Toshimitsu
T
D000818:Animals; D001515:Beer; D002243:Carbolines / Q000494:pharmacology*; D018736:DNA Adducts / Q000037:antagonists & inhibitors*; D008099:Liver / Q000737:chemistry*; D008168:Lung / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*
D002243:Carbolines; D018736:DNA Adducts; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole