Metabolism of benzo(e)pyrene by rat liver microsomal enzymes.
Metabolism of benzo(e)pyrene by rat liver microsomal enzymes.
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大鼠肝微粒体酶对苯并（e）芘的代谢。
DOI：
10.1093/carcin/1.2.165
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发表时间：
1980
期刊：
影响因子：
4.7
通讯作者：
Selkirk,JK
中科院分区：
文献类型：
--
作者：
MacLeod,MC;Levin,W;Conney,AH;Lehr,RE;Mansfield,BK;Jerina,DM;Selkirk,JK
用高压液相色谱法分离了[~ 3 H]-B[e]P与对照和诱导大鼠肝微粒体孵育后形成的苯并（e）芘（B[e]P）的代谢产物，并通过与合成标准品的保留时间、吸光度和荧光光谱的比较，对代谢产物进行了鉴定。产生的主要代谢产物为B[e]P-4，5-二氢二醇，占总代谢的20-30%，具体取决于微粒体的来源。随后是酚类代谢物（显示不是4-OH-、9-OH-或10-OH-B[e]P）。鉴定了B[e]P的一种可能的近似致癌衍生物，即B[e]P-9，10-二氢二醇，但发现其占总代谢物的比例不到1%。用纯化和重构的混合功能氧化酶系统获得了类似的结果。这些结果表明，反应性二醇-环氧化物，9，10-二羟基-11，12-环氧-9，10，11，-12-四氢-B [e]P，一种潜在的最终致癌代谢产物B[e] P的形成，是不受大鼠肝酶的青睐。这为在海湾地区化学致癌理论框架内B[e]P缺乏致癌性提供了部分解释。
Metabolites of benzo(e)pyrene (B[e]P) formed upon incubation of [3H]-B[e]P with hepatic microsomes from control and induced rats have been separated by high-pressure liquid chromatography and identified by comparison of retention times, absorbance and fluorescence spectra with those of synthetic standards. The major metabolite produced was B[e]P-4, 5-dihydrodiol, accounting for 20–30% of the total metabolism depending on the source of the microsomes. This was followed by a phenolic metabolite (shown not to be 4-OH-; 9-OH-; or 10-OH-B[e]P). A possible proximate carcinogenic derivative of B[e]P, B[e]P-9, 10-dihydrodiol, was identified, but was found to constitute less than 1% of the total metabolites. Similar results were obtained with a purified and reconstituted mixed-function oxidase system. In these later incubations, production of the dihydrodiols was dependent on the addition of purified epoxide hydrase to the incubation mixtures.These results suggest that formation of the reactive diol-epoxide, 9, 10-dihydroxy-11, 12-epoxy-9, 10, 11,-12-tetrahydro-B[e]P, a potential ultimate carcinogenic metabolite of B[e]P, is not favored by rat liver enzymes. This provides a partial explanation for the lack of carcinogenicity of B[e]P within the framework of the bay region theory of chemical carcinogenesis.