Comparative mutagenic efficiencies of the DNA adducts from the cooked-food-related mutagens Trp-P-2 and IQ in CHO cells.
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.
D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D007211:Indoles / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects*; D010053:Ovary; D011804:Quinolines / Q000633:toxicity*
D002243:Carbolines; D007211:Indoles; D011804:Quinolines; C017821:2-amino-3-methyl-9H-pyrido(2,3-b)indole; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA