Mutagenicity of N-OH-MOCA (4-amino-4'-hydroxylamino-bis-3,3'-dichlorodiphenylmethane) and PBQ (2-phenyl-1,4-benzoquinone) in human lymphoblastoid cells

Toxicol Lett. 1998 May;95(3):205-10. doi: 10.1016/s0378-4274(98)00039-3.

Abstract

The genotoxic potential of two occupationally significant chemicals, 4,4'-methylene-bis-2-chloroaniline (MOCA) and 2-phenyl-1,4-benzoquinone (PBQ), was explored by monitoring the induction of mutations at the HPRT locus of AHH-1 human lymphoblastoid cells. Exposure of AHH-1 cells to the putative carcinogenic metabolite of MOCA, N-OH-MOCA, induced a 6-fold increase in mutant frequency and resulted in base pair substitutions primarily at A:T base pairs. In contrast, exposure to PBQ did not result in an increased mutant frequency although this compound was significantly more cytotoxic than N-OH-MOCA at equimolar doses. The induction of mutations at A:T sites by N-OH-MOCA is consistent with the type of DNA damage known to be produced by MOCA and provides a specific marker of genotoxic damage for exposed populations.

MeSH terms

  • Benzoquinones / toxicity*
  • Carcinogens / toxicity*
  • DNA / analysis
  • DNA / drug effects
  • DNA / genetics
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Lymphocytes / drug effects
  • Lymphocytes / pathology*
  • Methylenebis(chloroaniline) / analogs & derivatives*
  • Methylenebis(chloroaniline) / toxicity
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Benzoquinones
  • Carcinogens
  • Mutagens
  • phenylbenzoquinone
  • Methylenebis(chloroaniline)
  • DNA
  • 5-hydroxy-3,3'-dichloro-4,4'-diaminodiphenylmethane-5-sulfate
  • Hypoxanthine Phosphoribosyltransferase