Oxidative stress in the metabolism of estrogens leading to cancer initiation: Prevention by specific antioxidants

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Oxidative metabolism of the estrogens estrone (E1) and estradiol (E2) is the critical event in the initiation of cancer by estrogens. E1 and E2 are oxidized by cytochrome P450 (CYP) to the catechol estrogens 2-OHE1(E2) and 4-OHE1(E 2) and then to the catechol estrogen quinones, which react with DNA to form estrogen-DNA adducts. The E1(E2)-3,4-quinones [E1(E2)-3,4-Q] react predominantly with DNA to form the depurinating adducts 4-OHE1(E2)-1-N3Ade and 4-OHE 1(E2)-1-N7Gua. The resulting apurinic sites in the DNA can generate mutations leading to the initiation of cancer. Estrogen metabolism becomes unbalanced when expression of the activating enzymes CYP19 (aromatase) and CYP1B1 is higher and expression of the protective enzymes catechol-O-methyltransferase and quinone reductase is lower. In this case, larger amounts of adducts are formed, and the risk of initiating cancer is greater. Women at high risk of developing breast cancer, or diagnosed with the disease, have higher levels of estrogen-DNA adducts than women at normal risk. These results and others in humans and cell culture indicate that formation of estrogen-DNA adducts is a critical event in the initiation of cancer. Two antioxidant compounds, N-acetylcysteine and resveratrol, efficiently block formation of estrogen-DNA adducts and, thus, are promising agents to prevent cancer.

Original languageEnglish (US)
Title of host publicationOxidative Stress
Subtitle of host publicationDiagnostics, Prevention, and Therapy
PublisherAmerican Chemical Society
Pages83-98
Number of pages16
ISBN (Print)9780841226838
DOIs
StatePublished - Nov 17 2011

Publication series

NameACS Symposium Series
Volume1083
ISSN (Print)0097-6156
ISSN (Electronic)1947-5918

Fingerprint

Oxidative stress
Antioxidants
Metabolism
Estrogens
DNA Adducts
Catechol Estrogens
Quinones
Aromatase
DNA
NAD(P)H Dehydrogenase (Quinone)
Enzymes
Resveratrol
Acetylcysteine
Catechol O-Methyltransferase
Estrone
Cell culture
Cytochrome P-450 Enzyme System
Estradiol

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Rogan, E. G., & Cavalieri, E. (2011). Oxidative stress in the metabolism of estrogens leading to cancer initiation: Prevention by specific antioxidants. In Oxidative Stress: Diagnostics, Prevention, and Therapy (pp. 83-98). (ACS Symposium Series; Vol. 1083). American Chemical Society. https://doi.org/10.1021/bk-2011-1083.ch004

Oxidative stress in the metabolism of estrogens leading to cancer initiation : Prevention by specific antioxidants. / Rogan, Eleanor G; Cavalieri, Ercole.

Oxidative Stress: Diagnostics, Prevention, and Therapy. American Chemical Society, 2011. p. 83-98 (ACS Symposium Series; Vol. 1083).

Research output: Chapter in Book/Report/Conference proceedingChapter

Rogan, EG & Cavalieri, E 2011, Oxidative stress in the metabolism of estrogens leading to cancer initiation: Prevention by specific antioxidants. in Oxidative Stress: Diagnostics, Prevention, and Therapy. ACS Symposium Series, vol. 1083, American Chemical Society, pp. 83-98. https://doi.org/10.1021/bk-2011-1083.ch004
Rogan EG, Cavalieri E. Oxidative stress in the metabolism of estrogens leading to cancer initiation: Prevention by specific antioxidants. In Oxidative Stress: Diagnostics, Prevention, and Therapy. American Chemical Society. 2011. p. 83-98. (ACS Symposium Series). https://doi.org/10.1021/bk-2011-1083.ch004
Rogan, Eleanor G ; Cavalieri, Ercole. / Oxidative stress in the metabolism of estrogens leading to cancer initiation : Prevention by specific antioxidants. Oxidative Stress: Diagnostics, Prevention, and Therapy. American Chemical Society, 2011. pp. 83-98 (ACS Symposium Series).
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