Induction by Estrogen Metabolite 16 ;-Hydroxyestrone of Genotoxic Damage and Aberrant Proliferation in Mouse Mammary Epithelial Cells

Abstract
Background: Estrogens are potent mammary tumor promoters influencing post-initiational events via epigenetic mechanisms. The upregulation (i.e., induction) of the C16α-hydroxylation pathway during 17β-estradiol (E 2 ) biotransformation has been associated with mammary cell transformation. The action of E 2 metabolites on tumorigenic transformation, however, is poorly understood. Purpose : The newly established mammary epithelial cell line C57/MG, derived from the C57BL mouse strain, was used to examine whether E 2 or its metabolites, 16-hydroxyestrone (16α-OHE 1 ) and estriol (E 3 ), function as initiators of mammary cell transformation. Methods : DNA repair (hydroxyurea-insensitive thymidine uptake), estrogen metabolism ( 3 H exchange to form 3 H 2 0), hyperproliferation (increased cell number), and acquisition of anchorage-independent

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