MUTAGENIC SYNERGY BETWEEN PARAOXON AND PLANT-ACTIVATED M-PHENYLENEDIAMINE OR 2-ACETOXYACETYLAMINOFLUORENE

Paraoxon (diethyl-p-nitrophenylphosphate) is the toxic, but non-mutage nic metabolite of the organophosphorus ester insecticide parathion. Al though this agent has been used as a deacetylase inhibitor in many stu dies, we discovered a mutagenic synergy when paraoxon was incubated wi th plant-activated m-phenylenediamine (mPDA) or with direct-acting 2-a cetoxyacetylaminofluorene (2AAAF) and S. typhimurium tester strains. U sing non-toxic concentrations of plant-activated mPDA and paraoxon a 1 0-fold increase in the mutant yield of S. typhimurium was observed. Th e mutagenicity of the plant-activated mPDA product required that O-ace tyl-transferase (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, T A98 and TA98/1,8-DNP6 regardless of their OAT activity. This mutagenic synergy is dependent upon the presence of an activated acetylated for m of the arylamine. The data presented here demonstrate that this muta genic synergy is limited to paraoxon and not to the parent compound (p arathion) or to a major metabolite of parathion (p-nitrophenol). (C) 1 996 Wiley-Liss, Inc.