Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells.
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.
Satou
Kazuya
K
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Sapporo 060-0812, Japan.
Kawai
Kazuaki
K
Kasai
Hiroshi
H
Harashima
Hideyoshi
H
Kamiya
Hiroyuki
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D002522:Chlorocebus aethiops; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000633:toxicity*; D029968:Escherichia coli Proteins / Q000235:genetics; D008081:Liposomes / Q000737:chemistry; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D014162:Transfection
C521293:8-hydroxy-2'-deoxyguanosine 5'-triphosphate; D002412:Cations; D003848:Deoxyguanine Nucleotides; D029968:Escherichia coli Proteins; D008081:Liposomes; C503794:Suf E protein, E coli; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D004259:DNA-Directed DNA Polymerase