Involvement of nitroreductase and O-acetyltransferase on the mutagenicity of plant-activated benzidine and 4-aminobiphenyl

Young H. Ju, Michael Jacob Plewa

Research output: Contribution to journalArticlepeer-review

Abstract

Benzidine and 4-aminobiphenyl (4-ABP) are activated by intact plant cells and cell free TX1 MX into mutagenic metabolites that induce frameshift and base pair substitution mutations in Salmonella typhimurium. The plant activation of these agents is plant peroxidase-mediated and bacterial O-acetyltransferase (OAT) dependent. TX1MX-activated benzidine and 4-ABP were analyzed with S. typhimurium frameshift tester strains, YG1021, YG1024, TA98, TA98NR, TA98/1,8-DNP6, MP219, and base pair substitution tester strains, YG1026, YG1029, TA100, TA100NR, TA100TN:OAT, and MP208. Concentration ranges for benzidine and 4-ABP were 1-50 μM and 0.1-1 mM, respectively. This study was conducted to determine if the plant-activation of benzidine and 4-ABP Follows the prostaglandin H synthase-mediated activation pathway in mammals [Smith et al. [1992): Chem Res Toxical 5; 431-439]. In this model, benzidine is N-acetylated by S. typhimurium OAT. This acetylated product is a substrate for PHS and is converted into a 4-nitro product which is catalyzed by nitroreductase into a N-hydroxy intermediate. The pathway assigns a; specific role for nitroreductase in the activation of benzidine. By employing S. typhimurium strains that express different levels of OAT and/or nitroreductase, we determined that the plant-activation of benzidine and 4-ABP has an absolute requirement of bacterial OAT activity for the induction of frameshift mutations at hisD3052 and is required for the optimal mutagenic response at hisG46. Nitroreductase also plays a role in the plant activation of these agents. The data suggest that the plant activation of benzidine and 4-ABP generates at least two classes of proximal mutagenic intermediates. One class requires S. typhimurium OAT alone to be transformed into the ultimate mutagen and a second class requires both OAT and nitroreductase.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalEnvironmental and Molecular Mutagenesis
Volume30
Issue number3
DOIs
StatePublished - Nov 28 1997

Keywords

  • 4-aminobiphenyl
  • Benzidine
  • Classical nitroreductase
  • O-acetyltransferase
  • Plant activation
  • Salmonella typhimurium
  • TX1MX

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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