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

• Published in: Mutation research Vol. 149; no. 2; p. 249
• Main Authors: Brookman, K W, Salazar, E P, Thompson, L H
• Format: Journal Article
• Language: English
• Published: Netherlands 01.04.1985
• Subjects: Animals; Carbolines - toxicity; Cell Line; Chemical Phenomena; Chemistry; Cricetinae; Cricetulus; DNA - genetics; DNA Repair; Female; Indoles - toxicity; Mutation - drug effects; Ovary; Quinolines - toxicity
• ISSN: 0027-5107
• DOI: 10.1016/0027-5107(85)90031-4

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.