Methylglyoxal induces G:C to C:G and G:C to T:A transversions in the supF gene on a shuttle vector plasmid replicated in mammalian cells.
We previously reported that the majority of base-pair substitutions induced by an endogenous mutagen, methylglyoxal, were G:C-->T:A transversions and G:C-->A:T transitions in wild-type and nucleotide excision repair (NER)-deficient (uvrA or uvrC) Escherichia coli strains. To investigate the mutation spectrum of methylglyoxal in mammalian cells and to compare the spectrum with those detected in other experimental systems, we analyzed mutations in a bacterial suppressor tRNA (supF) gene in the shuttle vector plasmid pMY189. We treated pMY189 with methylglyoxal and immediately transfected it into simian COS-7 cells. The cytotoxicity and the mutation frequency (MF) increased according to the dose of methylglyoxal. In the mutants induced by methylglyoxal, multi-base deletions were predominant (50%), followed by base-pair substitutions (35%), in which 89% of the substitutions occurred at G:C sites. Among them, G:C-->C:G and G:C-->T:A transversions were predominant. The overall distribution of methylglyoxal-induced mutations detected in the supF gene was different from that for the spontaneous mutations. These results suggest that methylglyoxal may take part in causing G:C-->C:G and G:C-->T:A transversions in vivo.
Murata-Kamiya
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Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
Kamiya
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Kaji
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Kasai
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D000818:Animals; D020029:Base Pairing / Q000187:drug effects; D001483:Base Sequence; D019556:COS Cells / Q000187:drug effects*; D002522:Chlorocebus aethiops; D004926:Escherichia coli / Q000235:genetics; D016153:Genes, Suppressor / Q000187:drug effects*; D005822:Genetic Vectors / Q000235:genetics; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D017354:Point Mutation / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000494:pharmacology / Q000633:toxicity*; D017384:Sequence Deletion
D011765:Pyruvaldehyde