Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells |
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Authors: | Satou Kazuya Kawai Kazuaki Kasai Hiroshi Harashima Hideyoshi Kamiya Hiroyuki |
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Institution: | Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Sapporo 060-0812, Japan. |
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Abstract: | The mutagenicity of an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP), was examined using COS-7 cells. 8-OH-dGTP and supF shuttle plasmid DNA were cointroduced by means of cationic liposomes, and the DNAs replicated in the cells were recovered and then transfected into Escherichia coli. 8-OH-dGTP induced A:T-->C:G substitution mutations in the COS-7 cells. This result agrees with previous observations indicating that DNA polymerases misincorporate 8-OH-dGTP opposite A in vitro, and that the oxidized deoxyribonucleotide induces A:T-->C:G transversions in E. coli. These results constitute the first direct evidence to show that 8-OH-dGTP actually induces mutations in living mammalian cells. |
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Keywords: | Reactive oxygen species 8-Hydroxy-dGTP Mutation Mammalian cells |
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