Comparative mutagenic efficiencies of the DNA adducts from the cooked-food-related mutagens Trp-P-2 and IQ in CHO cells

Mutat Res. 1985 Apr;149(2):249-55. doi: 10.1016/0027-5107(85)90031-4.

Abstract

The relationship between DNA-adduct formation and mutagenicity of two heterocyclic aromatic amines associated with cooked foods was determined in a CHO cell strain lacking nucleotide excision repair. Cells were exposed to tritiated IQ (2-amino-3-methylimidazo[4,5-f]quinoline) or Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) supplemented with hamster S9 microsomal fraction for metabolic activation. DNA from nuclei was isolated by DNAase-mediated elution from polycarbonate filters after RNAase and proteinase treatment. The presumed metabolites of both compounds bound to DNA in a dose-dependent fashion. Although the dose required to produce 50% cell killing was 15 times higher for IQ than Trp-P-2, the amount of radioactive material bound to DNA at that dose was about 10-fold lower with IQ. When mutations at the hprt and aprt loci were compared with the estimated levels of adducts, the calculated mutagenic efficiency of the adducts was about 4 mutations per 1000 adducts for both compounds, assuming a target sequence of 1000 base pairs for either locus. We conclude that IQ is acting as a weak mutagen in this system because its extracellular metabolites either do not reach or do not react efficiently with the DNA of the CHO cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbolines / toxicity*
  • Cell Line
  • Chemical Phenomena
  • Chemistry
  • Cricetinae
  • Cricetulus
  • DNA / genetics*
  • DNA Repair
  • Female
  • Indoles / toxicity*
  • Mutation / drug effects*
  • Ovary
  • Quinolines / toxicity*

Substances

  • Carbolines
  • Indoles
  • Quinolines
  • 2-amino-3-methyl-9H-pyrido(2,3-b)indole
  • 2-amino-3-methylimidazo(4,5-f)quinoline
  • DNA