Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells

Free Radic Biol Med. 2007 May 15;42(10):1552-60. doi: 10.1016/j.freeradbiomed.2007.02.024. Epub 2007 Feb 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • COS Cells
  • Cations / chemistry
  • Chlorocebus aethiops
  • DNA / drug effects*
  • DNA / genetics
  • DNA Replication
  • DNA-Directed DNA Polymerase / metabolism
  • Deoxyguanine Nucleotides / toxicity*
  • Escherichia coli Proteins / genetics
  • Liposomes / chemistry
  • Mutagenesis*
  • Mutation
  • Plasmids / chemistry
  • Plasmids / drug effects
  • Plasmids / genetics
  • Transfection

Substances

  • 8-hydroxy-2'-deoxyguanosine 5'-triphosphate
  • Cations
  • Deoxyguanine Nucleotides
  • Escherichia coli Proteins
  • Liposomes
  • Suf E protein, E coli
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • DNA-Directed DNA Polymerase