Distlerath L M, Loper J C, Tabor M W
Biochem Pharmacol. 1983 Dec 15;32(24):3739-48. doi: 10.1016/0006-2952(83)90144-2.
Metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone, MTP) is used as an inhibitor of cytochrome P-450 enzymes, particularly those induced by phenobarbital (PB). We examined the effects of MTP on the microsomal dependent mutagenesis of a newly isolated promutagen, 3-(2-chloroethoxy)-1,2-dichloropropene (CP), three S-chloroallyl thiocarbamate herbicides, and four model promutagens aflatoxin B1 (AFB), 2-acetylaminofluorene (2AAF), 2-aminoanthracene (2AA) and benzo[a]pyrene (BP). Salmonella tester strains TA98, TA100 and TA1535 and liver microsomal preparations (S9) from rats induced with PB or Aroclor 1254 (PCB) were employed. For statistical analysis, mutagenesis data were transformed and subjected to two-way analysis of variance. Metyrapone alone was not mutagenic in the absence or presence of S9. In a dose-dependent manner, MTP inhibited mutagenesis of AFB for strains TA98 and TA100 and enhanced mutagenesis of 2AAF, 2AA and BP for these strains. 3-(2-Chloroethoxy)-1, 2-dichloropropene and the herbicides diallate, triallate and sulfallate are all chloroallyl ethers. They are similar in their mutagenesis for Salmonella with respect to strain specificity, mutagenic potency, and requirement for activation by specifically-induced microsomes. Metyrapone inhibited the mutagenesis of CP, triallate and sulfallate for strain TA100 in the presence of either PB- or PCB-induced S9, and had no apparent effect on diallate mutagenesis; the same results were obtained for TA1535 with PCB-induced S9. On this basis, the mutagenic activation of diallate appears to be different from that of the other chloroallyl ethers tested. Our results indicate that MTP can inhibit as well as enhance microsomal dependent mutagenesis for Salmonella. We conclude that MTP may be a useful tool in characterizing pathways for promutagen activation.
甲吡酮（2-甲基-1,2-二-3-吡啶基-1-丙酮，MTP）用作细胞色素P-450酶的抑制剂，尤其是那些由苯巴比妥（PB）诱导的酶。我们研究了MTP对新分离的前诱变剂3-(2-氯乙氧基)-1,2-二氯丙烯（CP）、三种S-氯烯丙基硫代氨基甲酸酯类除草剂以及四种模型前诱变剂黄曲霉毒素B1（AFB）、2-乙酰氨基芴（2AAF）、2-氨基蒽（2AA）和苯并[a]芘（BP）的微粒体依赖性诱变的影响。使用了鼠伤寒沙门氏菌测试菌株TA98、TA100和TA1535以及用PB或艾氏剂1254（多氯联苯）诱导的大鼠肝脏微粒体制剂（S9）。为了进行统计分析，对诱变数据进行转换并进行双向方差分析。单独的甲吡酮在不存在或存在S9的情况下都没有致突变性。MTP以剂量依赖性方式抑制了TA98和TA100菌株对AFB的诱变，并增强了这些菌株对2AAF、2AA和BP的诱变。3-(2-氯乙氧基)-1,2-二氯丙烯以及除草剂燕麦敌、三唑酮和异硫氰酸烯丙酯都是氯烯丙基醚。它们在对鼠伤寒沙门氏菌的诱变方面，在菌株特异性、诱变效力以及对特异性诱导微粒体激活的需求方面相似。在存在PB或多氯联苯诱导的S9的情况下，甲吡酮抑制了TA100菌株对CP、三唑酮和异硫氰酸烯丙酯的诱变，并且对燕麦敌诱变没有明显影响；对于用多氯联苯诱导的S9的TA1535也得到了相同的结果。在此基础上，燕麦敌的诱变激活似乎与所测试的其他氯烯丙基醚不同。我们的结果表明，MTP可以抑制以及增强鼠伤寒沙门氏菌的微粒体依赖性诱变。我们得出结论，MTP可能是表征前诱变剂激活途径的有用工具。
