Mutagenic synergy between paraoxon and plant-activated m-phenylenediamine or 2-acetoxyacetylaminofluorene.
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).
Gichner
T
T
Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Prague.
Veleminský
J
J
Wagner
E D
ED
Plewa
M J
MJ
D000099:Acetoxyacetylaminofluorene / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology* / Q000633:toxicity; D010261:Paraoxon / Q000494:pharmacology*; D010655:Phenylenediamines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D010936:Plant Extracts / Q000378:metabolism; D010947:Plants, Toxic; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D014026:Nicotiana / Q000378:metabolism*
D016587:Antimutagenic Agents; D004791:Enzyme Inhibitors; D009153:Mutagens; D010655:Phenylenediamines; D010936:Plant Extracts; D011355:Prodrugs; D000099:Acetoxyacetylaminofluorene; D000123:Acetyltransferases; D000581:Amidohydrolases; C008381:3-phenylenediamine; D010261:Paraoxon