Initiation of cancer and other diseases by catechol ortho-quinones: a unifying mechanism

Cell Mol Life Sci. 2002 Apr;59(4):665-81. doi: 10.1007/s00018-002-8456-0.


Exposure to estrogens is a risk factor for breast and other human cancers. Initiation of breast, prostate and other cancers has been hypothesized to result from reaction of specific estrogen metabolites, catechol estrogen-3,4-quinones, with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine by 1,4-Michael addition. The catechol of the carcinogenic synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts with DNA to form depurinating adducts at the N-7 of guanine and N-3 of adenine. The catecholamine dopamine and the metabolite catechol (1,2-dihydroxybenzene) of the leukemogen benzene can also be oxidized to their quinones, which react with DNA to form predominantly analogous depurinating adducts. Apurinic sites formed by depurinating adducts are converted into tumor-initiating mutations by error-prone repair. These mutations could initiate cancer by estrogens and benzene, and Parkinson's disease by the neurotransmitter dopamine. These data suggest a unifying molecular mechanism of initiation for many cancers and neurodegenerative diseases and lay the groundwork for designing strategies to assess risk and prevent these diseases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Breast Neoplasms / chemically induced
  • Cricetinae
  • DNA Adducts / chemistry
  • DNA Adducts / metabolism
  • DNA Repair
  • Estrogens / chemistry
  • Estrogens / metabolism
  • Estrogens, Catechol / chemistry
  • Estrogens, Catechol / metabolism*
  • Estrogens, Catechol / toxicity
  • Female
  • Humans
  • Mice
  • Models, Genetic*
  • Mutagens / chemistry
  • Mutagens / metabolism*
  • Mutagens / toxicity
  • Neoplasms / chemically induced*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / chemically induced
  • Quinones / chemistry
  • Quinones / metabolism
  • Receptors, Estrogen / physiology


  • DNA Adducts
  • Estrogens
  • Estrogens, Catechol
  • Mutagens
  • Quinones
  • Receptors, Estrogen