Nesnow S, Lasley J, Curti S, Ross J, Nelson G, Sangaiah R, Gold A
Carcinogenesis and Metabolism Branch, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Cancer Res. 1991 Nov 15;51(22):6163-9.
Benz[j]aceanthrylene (B[j]A), a cyclopenta-fused polycyclic aromatic hydrocarbon related to 3-methylcholanthrene, has been studied to identify the major routes of metabolic activation in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. Previous studies have reported that the major (55% of total) B[j]A metabolite formed by C3H10T1/2 cells was (+/-)-trans-9,10-dihydro-9,10-dihydroxy-B[j]A (B[j]A-9,10-diol), the dihydrodiol in the bay-region ring, with moderate amounts (14% of total) of (+/-)-trans-1,2-dihydro-1,2-dihydroxy-B[j]A (B[j]A-1,2-diol), the cyclopenta-ring dihydrodiol. The morphological transforming activities of three potential intermediates formed by metabolism of B[j]A by C3H10T1/2 cells, (+/-)-anti-trans-9,10-dihydro-9,10-dihydroxy-B[j]A-7,8-oxide (B[j]A-diol-epoxide), B[j]A-9,10-oxide, and B[j]A-1,2-oxide as well as the two B[j]A-dihydrodiols were examined. B[j]A, B[j]A-diol-epoxide, B[j]A-1,2-oxide, and B[j]A-9,10-diol were found to have moderate to strong activities with B[j]A-diol-epoxide the most active compared to B[j]A, while B[j]A-1,2-diol was inactive. B[j]A-9,10-oxide was found to be a weak transforming agent. At 0.5 microgram/ml, the following percentage of dishes with type II or III foci were observed: B[j]A, 59%; B[j]A-diol-epoxide, 75%; B[j]A-1,2-oxide, 25%; and B[j]A-9,10-diol, 17%. DNA adducts of B[j]A, B[j]A-9,10-diol, B[j]A-diol-epoxide, B[j]A-9,10-oxide, and B[j]A-1,2-oxide in C3H10T1/2 cells were isolated, separated, identified, and quantitated using the 32P-postlabeling method. B[j]A forms two major groups of adducts: one group of adducts is the result of the interaction of B[j]A-1,2-oxide with 2'-deoxyguanosine and 2'-deoxyadenosine; the second group of adducts is a result of the interaction of B[j]A-diol-epoxide with 2'-deoxyguanosine and 2'-deoxyadenosine. Qualitative and quantitative analysis of the postlabeling data suggests that B[j]A is metabolically activated by two distinct routes, the bay-region diol-epoxide route and the cyclopenta-ring oxide route, the former being the most significant.
苯并[j]并四苯（B[j]A）是一种与3-甲基胆蒽相关的环戊稠合多环芳烃，已对其在可转化的C3H10T1/2CL8（C3H10T1/2）小鼠胚胎成纤维细胞培养物中的主要代谢活化途径进行了研究。先前的研究报道，C3H10T1/2细胞形成的主要B[j]A代谢物（占总量的55%）是（±）-反式-9,10-二氢-9,10-二羟基-B[j]A（B[j]A-9,10-二醇），即湾区环中的二氢二醇，还有适量（占总量的14%）的（±）-反式-1,2-二氢-1,2-二羟基-B[j]A（B[j]A-1,2-二醇），即环戊环二氢二醇。研究了C3H10T1/2细胞对B[j]A进行代谢形成的三种潜在中间体（±）-反式-9,10-二氢-9,10-二羟基-B[j]A-7,8-氧化物（B[j]A-二醇环氧化物）、B[j]A-9,10-氧化物和B[j]A-1,2-氧化物以及两种B[j]A-二氢二醇的形态转化活性。发现B[j]A、B[j]A-二醇环氧化物、B[j]A-1,2-氧化物和B[j]A-9,10-二醇具有中度到强的活性，其中B[j]A-二醇环氧化物的活性最强，而B[j]A-1,2-二醇无活性。发现B[j]A-9,10-氧化物是一种弱转化剂。在0.5微克/毫升时，观察到具有II型或III型病灶的培养皿的以下百分比：B[j]A为59%；B[j]A-二醇环氧化物为75%；B[j]A-1,2-氧化物为25%；B[j]A-9,10-二醇为17%。使用32P后标记法分离、分离、鉴定并定量了C3H10T1/2细胞中B[j]A、B[j]A-9,10-二醇、B[j]A-二醇环氧化物、B[j]A-9,10-氧化物和B[j]A-1,2-氧化物的DNA加合物。B[j]A形成两类主要加合物：一类加合物是B[j]A-1,2-氧化物与2'-脱氧鸟苷和2'-脱氧腺苷相互作用的结果；第二类加合物是B[j]A-二醇环氧化物与2'-脱氧鸟苷和2'-脱氧腺苷相互作用的结果。对后标记数据的定性和定量分析表明，B[j]A通过两条不同的途径进行代谢活化，即湾区二醇环氧化物途径和环戊环氧化物途径，前者最为重要。
