Mutagenic synergy between paraoxon and plant-activated m-phenylenediamine or 2-acetoxyacetylaminofluorene

• Published in: Environmental and molecular mutagenesis Vol. 27; no. 1; pp. 59 - 66
• Main Authors: Gichner, Tomáš, Velemínský, Jiří, Wagner, Elizabeth D., Plewa, Michael J.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 1996; Wiley-Liss
• Subjects: 2-acetoxyacetylaminofluorene; Acetoxyacetylaminofluorene - pharmacokinetics; Acetoxyacetylaminofluorene - pharmacology; Acetoxyacetylaminofluorene - toxicity; Acetyltransferases - antagonists & inhibitors; Amidohydrolases - antagonists & inhibitors; Antimutagenic Agents - pharmacology; Biological and medical sciences; Biotransformation - drug effects; diethyl-p-nitrophenylphosphate; Drug Synergism; Enzyme Inhibitors - pharmacology; Medical sciences; Mutagens - pharmacology; Mutagens - toxicity; Nicotiana - metabolism; paraoxon; Paraoxon - pharmacology; parathion; Pesticides, fertilizers and other agrochemicals toxicology; Phenylenediamines - pharmacokinetics; Phenylenediamines - pharmacology; Phenylenediamines - toxicity; Plant Extracts - metabolism; plant-activation; Plants, Toxic; Prodrugs - pharmacokinetics; Prodrugs - pharmacology; Prodrugs - toxicity; promutagenic m-phenylenediamine; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; synergic effect; tobacco suspension cells; Toxicology; Insecticide; Comutagen; Metabolite; Mutagenicity testing; Toxicity; Polycyclic aromatic compound; Metabolism; Salmonella typhimurium; Synergism; Phenylenediamine; Metabolic activation; Bacteria; Organophosphorus compounds; Mutation; Enterobacteriaceae
• ISSN: 0893-6692; 1098-2280
• 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 organo‐phosphorus 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). © 1996 Wiley‐Liss, Inc.