Genotoxicity assessment of aromatic amines and amides in genetically engineered V79 cells

Mutat Res. 1994 Dec;341(2):93-100. doi: 10.1016/0165-1218(94)90091-4.

Abstract

A genetically engineered V79 cell line expressing rat CYP1A2 and another cell line expressing rat CYP1A2 as well as endogenous acetyltransferase activity, as well as CYP-deficient parental V79 cell lines, were used to assess the genotoxicity of the aromatic amines and amides 2-aminoanthracene, 2-aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline, with chromosomal aberrations and sister chromatid exchanges as the end-points. None of the test compounds showed a clear effect on the frequency of chromosomal aberrations in any cell line used. Sister chromatid exchanges, however, were induced by 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene in the CYP1A2-proficient cells, but not in the CYP1A2-deficient cells. The presence of acetyltransferase activity enhanced the effect of 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene. 4-Acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline did not induce sister chromatid exchanges in the investigated cell lines. The use of cell lines with defined metabolic capabilities seems to be a valuable tool to study specific metabolic pathways important in the activation of procarcinogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / analogs & derivatives
  • 2-Acetylaminofluorene / toxicity
  • Animals
  • Anthracenes / toxicity
  • Biotransformation
  • Cell Line
  • Chromosome Aberrations
  • Cricetinae
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / physiology
  • Fluorenes / toxicity
  • Genetic Engineering
  • Mutagenicity Tests*
  • Mutagens / metabolism
  • Mutagens / toxicity*
  • Oxidoreductases / genetics
  • Oxidoreductases / physiology
  • Quinolines / toxicity
  • Rats
  • Sister Chromatid Exchange / drug effects

Substances

  • Anthracenes
  • Fluorenes
  • Mutagens
  • Quinolines
  • 2-amino-3-methylimidazo(4,5-f)quinoline
  • 2-aminofluorene
  • 2-anthramine
  • Cytochrome P-450 Enzyme System
  • 2-Acetylaminofluorene
  • Oxidoreductases
  • Cytochrome P-450 CYP1A2
  • 4-acetylaminofluorene