Jacob J, Schmoldt A, Hamann M, Raab G, Grimmer G
Cancer Lett. 1987 Jan;34(1):91-102. doi: 10.1016/0304-3835(87)90078-4.
The potencies of various xenobiotics for induction of monooxygenases and their influence on the rat liver microsomal metabolite profile of the environmentally relevant weak carcinogen, chrysene, was determined. Among the widely distributed chemicals, polychlorinated biphenyls (PCB) and preferentially 3,3',4,4'-tetrachlorobiphenyl as well as PAHs and their heterocyclic analogues such as benzo[a]pyrene, benzo[b]- and -[j]fluoranthene, indeno[1,2,3-cd]pyrene, dibenz[a,h]acridine, benzo[b]naphtho-[2,1-d]thiophene, and 5,6-benzoflavone were found to be potent inducers stimulating the formation of the proximate, and some of them also the ultimate carcinogen of chrysene. Lindane, carbaryl, DDT, and pentachlorophenol were found to be inefficient or weak inducers. With the exception of phenobarbital no inducers were found among the pharmaceuticals investigated. Sex-dependent metabolism was found for Wistar-rats. No 1,2-oxidation was observed in females, and turnover rates were lower than in males. These findings confirm the results previously obtained with benz[a]anthracene as substrate. The inducing potencies of various compounds tested were similar for both of these substrates. It is interesting to note that in most cases the same effective xenobiotic induces the bay-region diolepoxide in both, chrysene and benz[a]anthracene.
测定了各种外源性物质对单加氧酶的诱导能力及其对环境相关弱致癌物芘的大鼠肝脏微粒体代谢产物谱的影响。在广泛分布的化学物质中,发现多氯联苯(PCB),尤其是3,3',4,4'-四氯联苯以及多环芳烃及其杂环类似物,如苯并[a]芘、苯并[b]-和-[j]荧蒽、茚并[1,2,3-cd]芘、二苯并[a,h]吖啶、苯并[b]萘并-[2,1-d]噻吩和5,6-苯并黄酮是有效的诱导剂,可刺激芘的近端致癌物以及其中一些还包括终极致癌物的形成。林丹、西维因、滴滴涕和五氯苯酚被发现是低效或弱诱导剂。在所研究的药物中,除苯巴比妥外未发现诱导剂。在Wistar大鼠中发现了性别依赖性代谢。在雌性大鼠中未观察到1,2-氧化,其周转率低于雄性大鼠。这些发现证实了先前以苯并[a]蒽为底物所获得的结果。对于这两种底物,所测试的各种化合物的诱导能力相似。有趣的是,在大多数情况下,相同的有效外源性物质在芘和苯并[a]蒽中均诱导湾区二氢二醇环氧化物的形成。