Glyoxal, a major product of DNA oxidation, induces mutations at G:C sites on a shuttle vector plasmid replicated in mammalian cells.
Glyoxal is a major product of DNA oxidation in which Fenton-type oxygen free radical-forming systems are involved. To determine the mutation spectrum of glyoxal in mammalian cells and to compare the spectrum with those observed in other experimental systems, we analyzed mutations in a bacterial suppressor tRNA gene (supF) in the shuttle vector plasmid pMY189. We treated pMY189 with glyoxal and immediately transfected it into simian COS-7 cells. The cytotoxicity and mutation frequency increased according to the dose of glyoxal. The majority of glyoxal-induced mutations (48%) were single-base substitutions. Eighty three percent of the single-base substitutions occurred at G:C base pairs. Among them, G:C-->T:A transversions were predominant, followed by G:C-->C:G transversions and G:C-->A:T transitions. A:T-->T:A transversions were also observed. Mutational hotspots within the supF gene were detected. These results suggest that glyoxal may play an important role in mutagenesis induced by oxygen free radicals.
Murata-Kamiya
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Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807, Japan.
Kamiya
H
H
Kaji
H
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Kasai
H
H
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D003596:Cytosine; D004261:DNA Replication; D005798:Genes, Bacterial; D016153:Genes, Suppressor / Q000235:genetics*; D005822:Genetic Vectors; D006037:Glyoxal / Q000494:pharmacology*; D006147:Guanine; D008322:Mammals; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides; D010957:Plasmids / Q000187:drug effects*; D017354:Point Mutation; D012343:RNA, Transfer / Q000096:biosynthesis*; D017384:Sequence Deletion; D014162:Transfection
D009153:Mutagens; D009838:Oligodeoxyribonucleotides; C096275:supF tRNA; D006037:Glyoxal; D006147:Guanine; D003596:Cytosine; D012343:RNA, Transfer