Initiation of cancer and other diseases by catechol ortho-quinones

A unifying mechanism

Research output: Contribution to journalReview article

86 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)665-681
Number of pages17
JournalCellular and Molecular Life Sciences
Volume59
Issue number4
DOIs
StatePublished - May 13 2002

Fingerprint

Quinones
Estrogens
Guanine
Adenine
Metabolites
Benzene
Dopamine
DNA
Hexestrol
Neurodegenerative diseases
Estradiol Congeners
Neoplasms
Breast
Diethylstilbestrol
Mutation
Catecholamines
Neurotransmitter Agents
Tumors
Repair
Neurodegenerative Diseases

Keywords

  • 1,4-Michael addition
  • Catechol estrogens
  • Catecholamines
  • Depurinating DNA adducts
  • Error-prone DNA repair
  • Estrogen homeostasis
  • Tumor initiation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Initiation of cancer and other diseases by catechol ortho-quinones : A unifying mechanism. / Cavalieri, Ercole; Rogan, Eleanor G; Chakravarti, D.

In: Cellular and Molecular Life Sciences, Vol. 59, No. 4, 13.05.2002, p. 665-681.

Research output: Contribution to journalReview article

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