Hollstein M, Talcott R, Wei E
J Natl Cancer Inst. 1978 Feb;60(2):405-10. doi: 10.1093/jnci/60.2.405.
Quinoline, a hepatocarcinogen in rats, and 23 quinoline derivatives were tested for mutagenic activity with the Ames Salmonella typhimurium assay. Quinoline, 5-hydroxyquinoline, and 8-hydroxyquinoline were mutagenic in strain TA 100 when Aroclor 1254-induced rat (male outbred Sprague-Dawley) liver homogenate was present in the incubation mixture. Enzyme preparations from rats pretreated with P-448-dependent aryl hydrocarbon hydroxylase inducers [3-methylcholanthrene (MCA) and beta-naphthoflavone] and MCA-treated "responsive" C57BL mice also metabolized quinoline to a mutagen, but phenobarbital and pregnenolone-16alpha-carbonitrile pretreatment did not yield active preparations. The mutagenicity of quinoline was blocked by the in vitro addition of menadione, butylated hydroxytoluene, alpha-naphthoflavone, vitamin A acetate, and glutathione to the test system. Depletion of glutathione by diethyl maleate pretreatment in vivo enhanced the mutagenic potential of the liver enzyme preparation. Mutagenic activity was correlated to the formation of water-soluble quinoline metabolites, and we suggested that the reactive quinoline intermediate is quinoline-2,3-epoxide. Microsomal enzymes isolated from human liver tissue, but not lung tissue, also converted quinoline to a mutagen.
喹啉是大鼠体内的一种肝癌致癌物，利用鼠伤寒沙门氏菌艾姆斯试验对喹啉及23种喹啉衍生物的致突变活性进行了检测。当在孵育混合物中加入用多氯联苯混合物1254诱导的大鼠（雄性远交斯普拉格-道利大鼠）肝匀浆时，喹啉、5-羟基喹啉和8-羟基喹啉在TA 100菌株中具有致突变性。用依赖P-448的芳烃羟化酶诱导剂[3-甲基胆蒽（MCA）和β-萘黄酮]预处理的大鼠以及经MCA处理的“反应性”C57BL小鼠的酶制剂也能将喹啉代谢为一种致突变物，但苯巴比妥和孕烯醇酮-16α-腈预处理未能产生有活性的制剂。在测试系统中体外添加甲萘醌、丁基羟基甲苯、α-萘黄酮、维生素A醋酸酯和谷胱甘肽可阻断喹啉的致突变性。体内用马来酸二乙酯预处理耗尽谷胱甘肽可增强肝酶制剂的致突变潜力。致突变活性与水溶性喹啉代谢物的形成相关，我们认为反应性喹啉中间体是喹啉-2,3-环氧化物。从人肝组织而非肺组织分离的微粒体酶也能将喹啉转化为一种致突变物。
