Amacher D E, Turner G N
Mutat Res. 1980 Dec;74(6):485-501. doi: 10.1016/0165-1161(80)90179-x.
Individual S9 microsomal fractions prepared from normal livers of 8 rodent species or strains and from 1 rat strain pretreated with Aroclor 1254, were used to metabolize the promutagens N-acetyl-2-aminofluorene, 1,2-benzanthracene, benzo[a]pyrene, and 3-methylcholanthrene to active forms during 3-h co-incubation in the presence of L5178Y/TK+/- cells. The 8 compatible S9 preparations all converted each of the 4 chemical carcinogens into active mutagens with varied efficiencies except for the Aroclor-induced rat S9/benzanthracene combination which produced only weak activity. Aroclor induction did not notably enhance the mutagenicity of benzo[a]pyrene or 3-methylcholanthrene beyond that activity mediated by the other non-induced preparations. Syrian hamster S9 and, to a lesser degree, C57BL/6J mouse S9 were exceptionally active in converting N-acetyl-2-aminofluorene to toxic and mutagenic metabolites. One source of Swiss mouse liver (Blu : Ha ICR) provided the most active S9 when tested with the 3 polycyclic aromatic hydrocarbons. In general, mutagenicity and cytotoxicity were roughly correlated within S9 + promutagen combinations. Almost all of the methylcholanthrene metabolizing activity was lost by the 12th week when Aroclor-induced rat S9 was held at -20 degrees C, yet this activity remained constant when similar S9 was stored at -80 degrees C for 14 weeks. Surprisingly, some S9 sources including the induced rat-liver preparation converted anthracene to a weak or border-line mutagen. The activation of both 1,2-benzanthracene and anthracene may be linked within each species or strain although Aroclor induction enhanced anthracene mutagenicity yet attenuated the mutagenicity of 1,2-benzanthracene. Collectively, these data underscore the current inchoate state of development for S9 coupled somatic cell mutation assays.
从8种啮齿动物物种或品系的正常肝脏以及用多氯联苯混合物1254预处理的1种大鼠品系制备的个体S9微粒体组分，在L5178Y/TK+/-细胞存在的情况下进行3小时共孵育期间，用于将前诱变剂N-乙酰-2-氨基芴、1,2-苯并蒽、苯并[a]芘和3-甲基胆蒽代谢为活性形式。除了多氯联苯混合物诱导的大鼠S9/苯并蒽组合产生的活性较弱外，8种兼容的S9制剂均以不同效率将4种化学致癌物中的每一种转化为活性诱变剂。多氯联苯混合物诱导并未显著增强苯并[a]芘或3-甲基胆蒽的诱变性，超过其他未诱导制剂介导的活性。叙利亚仓鼠S9以及在较小程度上的C57BL/6J小鼠S9在将N-乙酰-2-氨基芴转化为有毒和诱变代谢物方面异常活跃。在用3种多环芳烃测试时，一种瑞士小鼠肝脏来源（Blu : Ha ICR）提供了活性最高的S9。一般来说，S9 + 前诱变剂组合中的诱变性和细胞毒性大致相关。当多氯联苯混合物诱导的大鼠S9在-20℃保存时，几乎所有的甲基胆蒽代谢活性在第12周时丧失，但当类似的S9在-80℃保存14周时，该活性保持不变。令人惊讶的是，一些S9来源包括诱导的大鼠肝脏制剂将蒽转化为弱诱变剂或临界诱变剂。尽管多氯联苯混合物诱导增强了蒽的诱变性，但减弱了1,2-苯并蒽的诱变性，但1,2-苯并蒽和蒽的活化在每个物种或品系中可能是相关的。总体而言，这些数据强调了S9偶联体细胞突变试验目前尚处于初步发展阶段。
