Oxidative DNA damage induced by a metabolite of carcinogenic o-anisidine: enhancement of DNA damage and alteration in its sequence specificity by superoxide dismutase

Arch Biochem Biophys. 2001 May 1;389(1):49-56. doi: 10.1006/abbi.2001.2302.

Abstract

The mechanism of DNA damage by a metabolite of the carcinogen o-anisidine in the presence of metals was investigated by the DNA sequencing technique using 32P-labeled human DNA fragments. The o-anisidine metabolite, o-aminophenol, caused DNA damage in the presence of Cu(II). The DNA damage was inhibited by catalase and bathocuproine, suggesting the involvement of H2O2 and Cu(I). The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by o-aminophenol increased in the presence of Cu(II). We conclude that Cu(II)-mediated oxidative DNA damage by this o-anisidine metabolite seems to be relevant for the expression of the carcinogenicity of o-anisidine. o-Aminophenol plus Cu(II) caused preferential DNA damage at the 5'-site guanine of GG and GGG sequences. When CuZn-SOD or Mn-SOD was added, the DNA damage was enhanced and its predominant cleavage sites were changed into thymine and cytosine residues. We consider that SOD may increase the frequency of mutations due to DNA damage induced by o-aminophenol and thus increase its carcinogenic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aminophenols / metabolism
  • Aminophenols / pharmacology*
  • Aniline Compounds / metabolism*
  • Animals
  • Carcinogens / metabolism*
  • Catalase / pharmacology
  • Cattle
  • Chelating Agents / pharmacology
  • Copper / metabolism
  • Cytosine / chemistry
  • DNA / chemistry
  • DNA / drug effects
  • DNA Damage* / drug effects
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / biosynthesis
  • Deoxyguanosine / chemistry
  • Electron Spin Resonance Spectroscopy
  • Free Radical Scavengers / pharmacology
  • Genes, ras / drug effects
  • Genes, ras / genetics
  • Guanine / chemistry
  • Humans
  • Manganese / metabolism
  • Manganese / pharmacology
  • Oxidation-Reduction / drug effects
  • Phenanthrolines / pharmacology
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase / pharmacology
  • Thymine / chemistry
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Aminophenols
  • Aniline Compounds
  • Carcinogens
  • Chelating Agents
  • Free Radical Scavengers
  • Phenanthrolines
  • Tumor Suppressor Protein p53
  • 2-aminophenol
  • Manganese
  • Guanine
  • Copper
  • 8-Hydroxy-2'-Deoxyguanosine
  • Cytosine
  • DNA
  • bathocuproine
  • Catalase
  • Superoxide Dismutase
  • Deoxyguanosine
  • 2-anisidine
  • Thymine