Abstract
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a food carcinogen formed in cooked meats, can induce gene mutation at the hprt locus of CHO-K1 cells in the presence of hepatic S9 mix. To elucidate the molecular nature of IQ-induced mutation, we characterized the entire coding region of the hypoxanthine phosphoribosyltransferase gene of 23 independent mutants derived from IQ-treated CHO cells by direct sequencing of polymerase chain reaction-amplified cDNA. Ten of the 23 IQ-induced mutants examined contained single base substitutions; one mutant had three single-base substitutions. Among the base substitutions, G·C→C·G (six of 13) and A·T→C·G (three of 13) transversions predominated. Most of the base-substitution mutations occurred preferentially at a middle G and had a dA in their 3 ends. Of the 13 other mutations (56.5%), 12 missing one or more complete exons were splice-site mutations, and one mutant had a partial deletion of an exon. A high frequency of complete exon deletion (11 of 12) in exons 2.5 was observed. Interestingly, 75% of the mutants (nine of 12) with splice-site mutations were induced by IQ only at higher concentrations (300-500 μM). This was probably due to the occurrence of GC base-substitution mutations that affected hprt mRNA splicing, especially at the intron-exon boundaries.
Original language | English |
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Pages (from-to) | 122-127 |
Number of pages | 6 |
Journal | Molecular Carcinogenesis |
Volume | 13 |
Issue number | 2 |
DOIs | |
Publication status | Published - Jun 1995 |
Externally published | Yes |
Keywords
- 2‐amino‐3‐methylimidazo[4,5‐f]quinoline
- CHO‐K1 cells
- Mutational specificity
- hprt gene
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research