Catechol quinones of estrogens in the initiation of breast, prostate, and other human cancers: Keynote lecture

Ercole Cavalieri, Eleanor Rogan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

92 Scopus citations


Estrogens can be converted to electrophilic metabolites, particularly the catechol estrogen-3,4-quinones, estrone(estradiol)-3,4-quinone [E 1(E2)-3,4-Q], which react with DNA to form depurinating adducts. These adducts are released from DNA to generate apurinic sites. Error-prone repair of this damage leads to the mutations that initiate breast, prostate, and other types of cancer. The reaction of E1(E 2)-3,4-Q with DNA forms the depurinating adducts 4-hydroxyE 1(E2)-1-N3adenine [4-OHE1(E2)-1- N3Ade] and 4-OHE1(E2)-1-N7guanine(Gua). These two adducts constitute >99% of the total DNA adducts formed. The E1(E 2)-2,3-Q forms small amounts of the depurinating 2-OHE 1(E2)-6-N3Ade adducts. Reaction of the quinones with DNA occurs more abundantly when estrogen metabolism is unbalanced. Such an imbalance is the result of overexpression of estrogen-activating enzymes and/or deficient expression of deactivating (protective) enzymes. Excessive formation of E 1(E2)-3,4-Q is the result of this imbalance. Oxidation of catechols to semiquinones and quinones is a mechanism of tumor initiation not only for endogenous estrogens, but also for synthetic estrogens such as hexestrol and diethylstilbestrol, a human carcinogen. This mechanism is also involved in the initiation of leukemia by benzene, rat olfactory tumors by naphthalene, and neurodegenerative diseases such as Parkinson's disease by dopamine. In fact, dopamine quinone reacts with DNA similarly to the E 1(E2)-3,4-Q, forming analogous depurinating N3Ade and N7Gua adducts. The depurinating adducts that migrate from cells and can be found in body fluids can also serve as biomarkers of cancer risk. In fact, a higher level of estrogen-DNA adducts has been found in the urine of men with prostate cancer and in women with breast cancer compared to healthy controls. This unifying mechanism of the origin of cancer and other diseases suggests preventive strategies based on the level of depurinating DNA adducts that generate the first critical step in the initiation of diseases.

Original languageEnglish (US)
Title of host publicationEstrogens and Human Diseases
PublisherBlackwell Publishing Inc.
Number of pages16
ISBN (Print)1573316695, 9781573316699
StatePublished - Nov 2006

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Biomarkers of cancer risk
  • Catechol quinones
  • Depurinating DNA adducts
  • Genotoxicity of estrogens
  • Metabolism of estrogens
  • Mutagenicity of estrogens
  • Unifying mechanism of cancer initiation

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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