Mechanisms of oxidative DNA damage induced by carcinogenic arylamines

Front Biosci (Landmark Ed). 2011 Jan 1;16:1132-43. doi: 10.2741/3739.


Most arylamines are pro-carcinogens, and require metabolic activation to yield ultimate carcinogen metabolites. O-Acetylation of the N-hydroxy form of an arylamine yields an acetoxyarylamine, which can form a highly reactive arylnitrenium ion, the ultimate metabolite responsible for DNA adduct formation. However, we demonstrate here that the N-hydroxy and nitroso forms of arylamines can also induce DNA damage, including 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) lesions, via reactive oxygen species formation. The N-hydroxy and nitroso derivatives of carcinogenic arylamines may contribute to the carcinogenic process through H2O2 formation. N-Hydroxy derivatives induce metal-mediated DNA damage, with remarkable enhancement by NADH. Nitroso derivatives induce NADH-dependent DNA damage in the presence of metal ions. Hydroxy derivatives of arylamines formed by enzymatic hydroxylation or as o- or p-aminophenols can also induce DNA damage in the presence of metal ions. The autoxidation of o-phenylenediamine and several arylamine metabolites is accelerated in the presence of SOD or manganese, resulting in the enhancement of metal-mediated DNA damage. The oxidative DNA damage induced by arylamine compounds may participate in chemical carcinogenesis, in addition to DNA adduct formation.

Publication types

  • Review

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aminobiphenyl Compounds / adverse effects
  • Animals
  • Benzidines / adverse effects
  • Carcinogens / metabolism
  • Carcinogens / pharmacology*
  • DNA Adducts
  • DNA Damage*
  • Deoxyguanosine / adverse effects
  • Deoxyguanosine / analogs & derivatives
  • Humans
  • Neoplasms / chemically induced*
  • Oxidation-Reduction


  • Aminobiphenyl Compounds
  • Benzidines
  • Carcinogens
  • DNA Adducts
  • 4-biphenylamine
  • benzidine
  • N-hydroxy-4-aminobiphenyl
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine