8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis

J Toxicol Sci. 1991 Feb;16 Suppl 1:95-105. doi: 10.2131/jts.16.supplementi_95.

Abstract

Oxygen radicals have been suggested to be involved in mutation/carcinogenesis. The C-8 position of guanine residues in DNA is hydroxylated to produce 8-hydroxyguanine (8-OH-Gua) in DNA in vitro by various oxygen radical producing agents. The formation of 8-OH-Gua was also observed in cellular DNA in vivo by radiation or oxygen radical forming carcinogens. The 8-OH-Gua residue in DNA is often misread in the position of 8-OH-Gua residue itself but also at neighboring residues next to 8-OH-Gua. When second guanine in codon 12 was specifically replaced with 8-OH-Gua and transferred to NIH3T3, the recipient cells were transformed to malignant cell type. E. coli was found to contain an endonuclease which specifically recognizes 8-OH-Gua residue and cleave DNA strand before and after the modified base. The data obtained imply that 8-OH-Gua formed in DNA in vivo is recognized as an abnormal modified base which, if not repaired, play a role in the mediation of oxygen radical-involved mutation/carcinogenesis.

MeSH terms

  • Animals
  • Base Sequence
  • Carcinogens*
  • DNA Damage*
  • Endonucleases / metabolism
  • Free Radicals
  • Genes, ras / genetics
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Guanine / metabolism
  • Guanine / toxicity
  • Humans
  • In Vitro Techniques
  • Leukocytes / metabolism
  • Liver / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutagens*
  • Oxygen / chemistry
  • Oxygen / toxicity*
  • Transformation, Genetic

Substances

  • Carcinogens
  • Free Radicals
  • Mutagens
  • 8-hydroxyguanine
  • Guanine
  • Endonucleases
  • Oxygen