The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism
The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism
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DOI：
10.1093/carcin/19.8.1369
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发表时间：
1998-08-01
期刊：
影响因子：
4.7
通讯作者：
Schilter, B
中科院分区：
文献类型：
--
作者：
Cavin, C;Holzhäuser, D;Schilter, B
在动物模型中，已将二萜类化合物咖啡豆和咖啡豆酚（C&K）鉴定为存在于绿色和烘焙咖啡豆中的两种潜在的化学保护剂。在这项研究中，我们研究了C&K对黄曲霉毒素B1（AFB（1））代谢产物与DNA共价结合的影响。28和90天。在体外结合试验中，使用来自C& K处理的大鼠肝脏的S9和微粒体亚细胞组分观察到AFB（1）DNA结合的剂量依赖性抑制，在2300 p. p.m.时检测到显著抑制，并且在6200 p. p.m.的饮食C&K时，DNA加合物形成达到最大减少，接近对照值的50%，两种互补的机制可能占的化学预防作用的黄曲霉毒素pi的大鼠中的阿托伐他汀和卡胡韦醇。大鼠活化细胞色素P450的表达减少（CYP 2C 11和CYP 3A 2），以及谷胱甘肽-S-转移酶（GST）亚基GST Yc 2的表达的强烈诱导，已知GST Yc 2对AFB 1的最具遗传毒性的代谢物具有高度解毒作用。这些数据和先前证明的C&K对7，12-二甲基苯并[a]蒽（DMBA）在不同组织部位诱导的致癌作用表明这些咖啡成分对化学致癌作用的潜在广泛影响。
The diterpenes cafestol and kahweol (C&K) have been identified in animal models as two potentially chemoprotective agents present in green and roasted coffee beans. It has been postulated that these compounds may act as blocking agents by producing a co-ordinated modulation of multiple enzymes involved in carcinogen detoxification, In this study, we investigated the effects of C&K against the covalent binding of aflatoxin B1 (AFB(1)) metabolites to DNA, Male Sprague-Dawley rats were treated with increasing amounts of a mixture of C&K in the diet (0-6200 p.p.m.) for 28 and 90 days. A dose-dependent inhibition of AFB(1) DNA-binding was observed using S9 and microsomal subcellular fractions from C&K-treated rat liver in an in vitro binding assay, Significant inhibition was detected at 2300 p.p.m. and maximal reduction of DNA adduct formation to nearly 50% of the control value was achieved with 6200 p,p,m, of dietary C&K, Two complementary mechanisms may account for the chemopreventive action of cafestol and kahweol against aflatoxin pi in rats. A decrease in the expression of the rat activating cytochrome P450s (CYP2C11 and CYP3A2) was observed, as well as a strong induction of the expression of the glutathione-S-transferase (GST) subunit GST Yc2, which is known to detoxify highly the most genotoxic metabolite of AFB1, These data and the previously demonstrated effects of C&K against the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis at various tissue sites suggest the potential widespread effect of these coffee components against chemical carcinogenesis.