Paraoxon-mediated antimutagenicity and mutagenic synergy of dietary arylamines assayed in Salmonella typhimurium and human lymphocytes

Michael Jacob Plewa, Elizabeth D. Wagner, Tian Wei Yu, Diana Anderson

Research output: Contribution to journalArticlepeer-review

Abstract

There is nearly universal exposure to organophosphorus ester insecticides and aromatic amines. Previously we reported that specific aromatic amines and paraoxon induced enhanced mutagenic responses in several S. typhimurium tester strains. In this study we demonstrated that paraoxon could alter the genotoxic potency of mammalian activated m-phenylenediamine (mPDA) and the dietary carcinogens 2-amino-3-methylimidazo-(4,5-f)quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) as measured in S. typhimurium and in human lymphocytes. Paraoxon alone was not genotoxic in any of the assays. All three aromatic amines exhibited paraoxon-mediated mutagenic synergy when assayed with S. typhimurium strain YG1024. However, using the single cell gel electrophoresis (Comet) assay with lymphocytes, a paraoxon concentration-dependent genotoxic synergy was induced with mPDA. A bimodal response was observed with lymphocytes treated with a constant amount of IQ or PhIP and with 1 to 500 μM paraoxon. At low paraoxon concentrations a significant increase in the comet tail moment value was induced when compared with the cells treated with IQ or PhIP alone. At higher paraoxon concentrations a significant antigenotoxic response was observed. These data demonstrate that an environmental agent such as paraoxon, can induce both genotoxic synergy and antigenotoxicity in human cells depending on its concentration. This result raises the concern of the environmental effects of organophosphorus ester insecticides under real- world conditions where people are exposed to a multitude of genotoxic agents.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume16
Issue number4
StatePublished - Jan 1 1997

Keywords

  • Antigenotoxicity
  • Antimutagens
  • Comet assay
  • Genotoxicity
  • Mutagens
  • Paraoxon
  • Single cell gel electrophoresis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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