Gichner T, Veleminský J, Wagner E D, Plewa M J
Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Prague.
Environ Mol Mutagen. 1996;27(1):59-66. doi: 10.1002/(SICI)1098-2280(1996)27:1<59::AID-EM8>3.0.CO;2-9.
Paraoxon (diethyl-p-nitrophenylphosphate) is the toxic, but non-mutagenic metabolite of the organophosphorus ester insecticide parathion. Although this agent has been used as a deacetylase inhibitor in many studies, we discovered a mutagenic synergy when paraoxon was incubated with plant-activated m-phenylenediamine (mPDA) or with direct-acting 2-acetoxyacetylaminofluorene (2AAAF) and S. typhimurium tester strains. Using non-toxic concentrations of plant-activated mPDA and paraoxon a 10-fold increase in the mutant yield of S. typhimurium was observed. The mutagenicity of the plant-activated mPDA product required that O-acetyltransferase (OAT) be expressed by the S. typhimurium tester strain. However, the paraoxon-dependent mutagenic synergy was observed using the direct-acting arylamine metabolite, 2AAAF, with strains YG1024, TA98 and TA98/1,8-DNP6 regardless of their OAT activity. This mutagenic synergy is dependent upon the presence of an activated acetylated form of the arylamine. The data presented here demonstrate that this mutagenic synergy is limited to paraoxon and not to the parent compound (parathion) or to a major metabolite of parathion (p-nitrophenol).
对氧磷（二乙基 - 对硝基苯基磷酸酯）是有机磷酯类杀虫剂对硫磷的有毒但无致突变性的代谢产物。尽管在许多研究中该试剂被用作脱乙酰酶抑制剂，但我们发现，当对氧磷与植物激活的间苯二胺（mPDA）或直接作用的2 - 乙酰氧基乙酰氨基芴（2AAAF）以及鼠伤寒沙门氏菌测试菌株一起孵育时，会产生诱变协同作用。使用无毒浓度的植物激活的mPDA和对氧磷时，观察到鼠伤寒沙门氏菌的突变产量增加了10倍。植物激活的mPDA产物的致突变性要求鼠伤寒沙门氏菌测试菌株表达O - 乙酰转移酶（OAT）。然而，无论其OAT活性如何，使用直接作用的芳胺代谢产物2AAAF与菌株YG1024、TA98和TA98/1,8 - DNP6观察到了对氧磷依赖性诱变协同作用。这种诱变协同作用取决于芳胺的活化乙酰化形式的存在。此处呈现的数据表明，这种诱变协同作用仅限于对氧磷，而不适用于母体化合物（对硫磷）或对硫磷的主要代谢产物（对硝基苯酚）。
