Guobaitis R J, Ellingham T J, Maddock M B
Mutat Res. 1986 Feb;164(1):59-70. doi: 10.1016/0165-1161(86)90042-7.
A series of experiments was designed to characterize the cytochrome P-450-dependent activation of 7 genotoxic carcinogens in the Salmonella preincubation assay by hepatic postmitochondrial fractions (S9) from the oyster toadfish and the Americal eel and by renal S9 from the toadfish. Significant S9-dependent mutagenicity was observed for benzo[a]pyrene (BAP), 2-aminoanthracene (2AA), aflatoxin B1 (AFB1), 7,12-dimethylbenz[a]anthracene (DMBA) and cyclophosphamide (CP) with hepatic S9 from untreated fish (UI S9) of both species and with renal S9 from untreated toadfish, although renal UI S9 was only marginally effective for activating AFB1. Neither UI S9 from toadfish liver or kidney nor that from eel liver consistently affected the direct mutagenicity of ethylene dibromide (EDB) or substantially activated dimethylnitrosamine (DMN). Pretreatment of toadfish with 3-methylcholanthrene (MC) decreased the mutagenicity of 2AA and increased the mutagenicities of BAP, AFB1 and DMBA, whereas, pretreatment of eels with MC increased the mutagenicities of BAP, 2AA and AFB1. Pretreatment of toadfish with Aroclor 1254 (AC) decreased the mutagenicity of AFB1 and increased the mutagenicity of 2AA, whereas, pretreatment of eels with AC increased the mutagenicities of BAP and DMBA. Pretreatment of toadfish with beta-napthoflavone (BNF) effected changes similar to those by pretreatment with MC except that the mutagenicity of AFB1 was not increased. Coincubation with 10(-4) M alpha-napthoflavone (ANF) decreased the mutagenicity of BAP mediated by toadfish MC and BNF S9 and eel AC S9 and decreased the mutagenicity of AFB1 mediated by toadfish MC and BNF S9 and by eel MC S9. Coincubation with ANF increased the mutagenicity of AFB1 mediated by toadfish and eel AC S9 and increased the mutagenicity of 2AA mediated by eel AC S9. Pretreatment of toadfish with MC, BNF and AC decreased the mutagenicity of 2AA mediated by renal S9 and ANF decreased the mutagenicity of 2AA mediated by renal UI and BNF S9. MC pretreatment of toadfish and eels and BNF pretreatment of toadfish induced BAP monooxygenase activity in hepatic microsomes. ANF (10(-4) M) inhibited the BAP monooxygenase activity of MC microsomes from toadfish and eels and of BNF microsomes from toadfish. The conjugation effectors diethyl maleate and salicylamide alone or combined had little or no effect on the mutagenicities of BAP and 2AA mediated by toadfish and eel UI and MC S9.(ABSTRACT TRUNCATED AT 400 WORDS)
设计了一系列实验，以表征在鼠伤寒沙门氏菌预培养试验中，来自牡蛎蟾鱼和美洲鳗鱼肝后线粒体组分（S9）以及蟾鱼肾S9对7种遗传毒性致癌物的细胞色素P - 450依赖性激活作用。在两种未处理鱼（UI S9）的肝S9以及未处理蟾鱼的肾S9中，观察到苯并[a]芘（BAP）、2 - 氨基蒽（2AA）、黄曲霉毒素B1（AFB1）、7,12 - 二甲基苯并[a]蒽（DMBA）和环磷酰胺（CP）具有显著的S9依赖性致突变性，尽管肾UI S9对AFB1的激活作用仅微效。来自蟾鱼肝或肾以及鳗鱼肝的UI S9均未持续影响1,2 - 二溴乙烷（EDB）的直接致突变性，也未显著激活二甲基亚硝胺（DMN）。用3 - 甲基胆蒽（MC）预处理蟾鱼会降低2AA的致突变性，并增加BAP、AFB1和DMBA的致突变性，而用MC预处理鳗鱼则会增加BAP、2AA和AFB1的致突变性。用多氯联苯混合物1254（AC）预处理蟾鱼会降低AFB1的致突变性并增加2AA的致突变性，而用AC预处理鳗鱼则会增加BAP和DMBA的致突变性。用β - 萘黄酮（BNF）预处理蟾鱼产生的变化与用MC预处理相似，只是AFB1的致突变性未增加。与10⁻⁴ M α - 萘黄酮（ANF）共孵育会降低由蟾鱼MC和BNF S9以及鳗鱼AC S9介导的BAP致突变性，也会降低由蟾鱼MC和BNF S9以及鳗鱼MC S9介导的AFB1致突变性。与ANF共孵育会增加由蟾鱼和鳗鱼AC S9介导的AFB1致突变性，以及由鳗鱼AC S9介导的2AA致突变性。用MC、BNF和AC预处理蟾鱼会降低肾S9介导的2AA致突变性，而ANF会降低肾UI和BNF S9介导的2AA致突变性。用MC预处理蟾鱼和鳗鱼以及用BNF预处理蟾鱼会诱导肝微粒体中的BAP单加氧酶活性。ANF（10⁻⁴ M）抑制了来自蟾鱼和鳗鱼的MC微粒体以及来自蟾鱼的BNF微粒体的BAP单加氧酶活性。共轭效应剂马来酸二乙酯和水杨酰胺单独或联合使用对由蟾鱼和鳗鱼UI以及MC S9介导的BAP和2AA的致突变性几乎没有影响。（摘要截于400字）
