Arimoto-Kobayashi Sakae, Ishida Rie, Nakai Yumi, Idei Chiho, Takata Jun, Takahashi Eizo, Okamoto Keinosuke, Negishi Tomoe, Konuma Toshimitsu
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Sciences, Okayama University, Japan.
Biol Pharm Bull. 2006 Jan;29(1):67-70. doi: 10.1248/bpb.29.67.
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.
对啤酒成分针对人类饮食中所含致癌物(即包括2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)在内的杂环胺(HCA))的抗原毒性潜力进行了评估。还研究了其中涉及的保护机制。在艾姆斯试验中发现啤酒样品可抑制HCA的致突变性。与在无啤酒溶液的情况下喂食PhIP的对照小鼠相比,以冻干并溶解的样品组成的啤酒溶液作为饮用水显著减少了小鼠结肠和肺中PhIP-DNA加合物的形成。此外,作为食品添加剂模拟物添加到饮食中的啤酒溶液显著减少了喂食PhIP的小鼠肝脏和肺中存在的DNA加合物数量。为了研究导致观察到的保护作用的机制,研究了啤酒溶液对HCA代谢酶的影响。分别使用7-乙氧基和7-甲氧基试卤灵通过脱乙基化和脱甲基化试验确定,啤酒溶液抑制了CYP1A1和CYP1A2的活性。考虑到啤酒对PhIP遗传毒性的总体抑制作用,本研究证实啤酒成分可干扰参与HCA代谢的酶活性,并随后抑制观察到的遗传毒性。本研究结果表明,啤酒成分在体内对杂环胺的遗传毒性作用具有保护能力。