Miller C H, Zhang Z, Hamilton S M, Teel R W
Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, CA 92350.
Cancer Lett. 1993 Nov 30;75(1):45-52. doi: 10.1016/0304-3835(93)90206-o.
Chemically-induced mutagenesis and carcinogenesis is modulated by various plant products, some of which are present in the human diet. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen in tobacco and tobacco smoke, is activated by microsomal enzymes. In this study, we investigated the effects of capsaicin on the in vitro metabolism of NNK. Capsaicin is the principal component of Capsicum fruits used widely by humans as a food additive. Liver microsomes from saline-injected, phenobarbital-induced and beta-naphthoflavone-induced hamsters were used. Microsomes from phenobarbital and beta-naphthoflavone-induced animals expressed decreased NNK reduction and enhanced pyridine-N-oxidation, but did not significantly alter alpha-carbon hydroxylation of NNK. Capsaicin (0.5 mM) inhibited the formation of all metabolites of NNK by all microsomal fractions and inhibited alpha-hydroxylation by phenobarbital-induced microsomes more than by either of the other two treatments. Our results suggest that capsaicin, as a naturally occurring dietary constituent, possesses antimutagenic and anticarcinogenic properties through the inhibition of xenobiotic metabolizing enzymes.
化学诱导的诱变和致癌作用受到多种植物产物的调节，其中一些存在于人类饮食中。4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是烟草和烟草烟雾中的一种强效致癌物，可被微粒体酶激活。在本研究中，我们研究了辣椒素对NNK体外代谢的影响。辣椒素是辣椒果实的主要成分，被人类广泛用作食品添加剂。使用了来自注射生理盐水、苯巴比妥诱导和β-萘黄酮诱导的仓鼠的肝微粒体。来自苯巴比妥和β-萘黄酮诱导动物的微粒体表现出NNK还原减少和吡啶-N-氧化增强，但未显著改变NNK的α-碳羟基化。辣椒素（0.5 mM）抑制了所有微粒体组分对NNK所有代谢产物的形成，并且对苯巴比妥诱导的微粒体α-羟基化的抑制作用比对其他两种处理中的任何一种都更强。我们的结果表明，辣椒素作为一种天然存在的饮食成分，通过抑制外源性代谢酶具有抗诱变和抗癌特性。
