Abstract

A growing number of studies indicate that breast cancer initiation is related to abnormal estrogen oxidation to form an excess of estrogen-3,4-quinones, which react with DNA to form depurinating adducts and induce mutations. This mechanism is often called estrogen genotoxicity. 4-Catechol estrogens, precursors of the estrogen-3,4-quinones, were previously shown to account for most of the transforming and tumorigenic activity. We examined whether estrogen-induced transformation can be reduced by inhibiting the oxidation of a 4-catechol estrogen to its quinone. We demonstrate that E6 cells (a normal mouse epithelial cell line) can be transformed by a single treatment with a catechol estrogen or its quinone. The transforming activities of 4-hydroxyestradiol and estradiol-3,4-quinone were comparable. N-Acetylcysteine, a common antioxidant, inhibited the oxidation of 4-hydroxyestradiol to the quinone and consequent formation of DNA adducts. It also drastically reduced estrogen-induced transformation of E6 cells. These results strongly implicate estrogen genotoxicity in mammary cell transformation. Since N-acetylcysteine is well tolerated in clinical studies, it may be a promising candidate for breast cancer prevention.

Original languageEnglish (US)
Pages (from-to)22-30
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume109
Issue number1-2
DOIs
StatePublished - Mar 1 2008

Fingerprint

Acetylcysteine
Estrogens
Breast
Epithelial Cells
Catechol Estrogens
Quinones
Oxidation
Breast Neoplasms
DNA Adducts
Antioxidants
Cell Line
Mutation
DNA
benzoquinone

Keywords

  • Catechol estrogen quinone
  • Mammary epithelial cells
  • N-acetylcysteine
  • Transformation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Reduction of estrogen-induced transformation of mouse mammary epithelial cells by N-acetylcysteine. / Venugopal, Divya; Zahid, Muhammad; Mailander, Paula C.; Meza, Jane L; Rogan, Eleanor G; Cavalieri, Ercole; Chakravarti, Dhrubajyoti.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 109, No. 1-2, 01.03.2008, p. 22-30.

Research output: Contribution to journalArticle

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