Newcomb K O, Sangaiah R, Gold A, Ball L M
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill 27599-7400.
Mutat Res. 1993 Jun;287(2):181-90. doi: 10.1016/0027-5107(93)90011-4.
Benz[j]aceanthrylene, a cyclopentafused polycylic aromatic hydrocarbon produced in combustion emissions, possesses a bay region and an etheno bridge which may both contribute to the overall genotoxicity of the compound. In order to assess the role of activation at the bay region, the precursor epoxide benz[j]aceanthrylene 9,10-oxide, its dehydration product 10-hydroxybenz[j]aceanthrylene, the key dihydrodiol 9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene and the bay-region diol-epoxide 7,8-epoxy-9,10-dihydroxy-7,8,9,10- tetrahydrobenz[j]aceanthrylene were evaluated in the bacterial histidine-reversion plate incorporation assay (Ames assay) with Salmonella typhimurium strain TA98. The diol-epoxide alone showed direct-acting mutagenicity (10 revertants per nmole), which was decreased by addition of exogenous metabolic activation (Aroclor 1254-treated rat-liver S9), whereas all the other compounds tested were activated by increasing concentrations of S9. The potency of the diol-epoxide was not sufficient to account for the activity of the parent compound. Identification by proton nuclear magnetic resonance and mass spectrometry of the major products of further metabolism by Aroclor 1254-treated rat-liver S9 of the bay region precursor dihydrodiol 9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene indicated that oxidation occurred predominantly at the etheno bridge, to give 9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene-2(1H)-one, arising by (non-enzymic) rearrangement of the etheno bridge epoxide and the tetrol 1,2,9,10-tetrahydroxy-1,2,9,10- tetrahydrobenz[j]aceanthrylene. The bay region tetrol 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenz[j] aceanthrylene was observed, implying further bay-region metabolism; re-aromatization of the benzo ring to benz[j]aceanthrylene-9,10-diol also occurred. Thus oxidation at the etheno bridge accounts for the majority of the activity of benz[j]aceanthrylene and its derivatives when Aroclor 1254-treated rat-liver S9 is used for exogenous metabolic activation.
苯并[j]ace蒽烯是一种在燃烧排放物中产生的环戊稠合多环芳烃，它具有一个湾区和一个乙烯桥，这两者都可能对该化合物的整体遗传毒性有贡献。为了评估湾区活化的作用，在鼠伤寒沙门氏菌TA98菌株的细菌组氨酸回复平板掺入试验（艾姆斯试验）中，对前体环氧化物苯并[j]ace蒽烯9,10-氧化物、其脱水产物10-羟基苯并[j]ace蒽烯、关键的二氢二醇9,10-二羟基-9,10-二氢苯并[j]ace蒽烯以及湾区二醇环氧化物7,8-环氧-9,10-二羟基-7,8,9,10-四氢苯并[j]ace蒽烯进行了评估。仅二醇环氧化物显示出直接作用的致突变性（每纳摩尔10个回复突变体），添加外源性代谢活化剂（Aroclor 1254处理的大鼠肝脏S9）后致突变性降低，而所有其他测试化合物在S9浓度增加时被活化。二醇环氧化物的效力不足以解释母体化合物的活性。通过质子核磁共振和质谱对Aroclor 1254处理的大鼠肝脏S9对湾区前体二氢二醇9,10-二羟基-9,10-二氢苯并[j]ace蒽烯进一步代谢的主要产物进行鉴定，结果表明氧化主要发生在乙烯桥上，生成9,10-二羟基-9,10-二氢苯并[j]ace蒽烯-2(1H)-酮，这是由乙烯桥环氧化物和四醇1,2,9,10-四羟基-1,2,9,10-四氢苯并[j]ace蒽烯的（非酶）重排产生的。观察到了湾区四醇7,8,9,10-四羟基-7,8,9,10-四氢苯并[j]ace蒽烯，这意味着在湾区有进一步的代谢；苯环也重排成了苯并[j]ace蒽烯-9,10-二醇。因此，当使用Aroclor 1254处理的大鼠肝脏S9进行外源性代谢活化时，乙烯桥上的氧化占苯并[j]ace蒽烯及其衍生物活性的大部分。
