Mutational specificity of 2-amino-3-methylimidazo-[4,5-f]quinoline in the hprt locus of CHO-K1 cells

✍ Scribed by Huei Lee; Ming-Kuei Shih

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 572 KB
• Volume: 13
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.2940130209

✦ Synopsis

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 59 mix. To elucidate the molecular nature of IQ‐induced mutation, we characterized the entire coding region of the hypoxanthine phosphoribosyl‐transferase 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→CG (six of 13) and A·T→CG (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. © 1995 Wiley‐Liss, Inc.