Journal Article

The ability of four catechol estrogens of 17β-estradiol and estrone to induce DNA adducts in Syrian hamster embryo fibroblasts

Eiichi Yagi, J.Carl Barrett and Takeki Tsutsui

in Carcinogenesis

Volume 22, issue 9, pages 1505-1510
Published in print September 2001 | ISSN: 0143-3334
Published online September 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.9.1505
The ability of four catechol estrogens of 17β-estradiol and estrone to induce DNA adducts in Syrian hamster embryo fibroblasts

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Catechol estrogens are considered critical intermediates in estrogen-induced carcinogenesis. We demonstrated previously that 17β-estradiol (E2), estrone (E1) and four of their catechol estrogens, 2- and 4-hydroxyestradiols (2- and 4-OHE2), and 2- and 4-hydroxyestrones (2- and 4-OHE1) induce morphological transformation in Syrian hamster embryo (SHE) fibroblasts, and the transforming abilities vary as follows: 4-OHE1 > 2-OHE1 > 4-OHE2 > 2-OHE2 │ E2, E1. To examine the involvement of catechol estrogens in the initiation of hormonal carcinogenesis, we studied the ability of E2, E1 and their catechol estrogens to induce DNA adducts in SHE cells by using a 32P-post-labeling assay. DNA adducts were detected in cells treated with each of all the catechol estrogens at concentrations of 10 μg/ml for 1 h and more. 2- or 4-OHE2 formed a single DNA adduct, which was chromatographically distinct from each other. In contrast, 2- or 4-OHE1 produced one major and one minor adduct, and the two adducts formed by each catechol estrogen exhibited identical mobilities on the chromatograms. Neither E2 nor E1 at concentrations up to 30 μg/ml induced DNA adducts. The abilities of the estrogens to induce DNA adducts were ranked as follows: 4-OHE1 > 2-OHE1 > 4-OHE2 > 2-OHE2 > > E2, E1, which corresponds well to the transforming and carcinogenic abilities of the estrogens. In addition, the level of DNA adducts induced by the catechol estrogens was markedly decreased by co-treatment of cells with the antioxidant L-ascorbic acid. The results indicate the possible involvement of oxidative metabolites of catechol estrogens of E2 and E1 in the initiation of endogenous estrogen-induced carcinogenesis.

Keywords: E2, 17β-estradiol; E1, estrone; 4-OHE2, 4-hydroxyestradiol; 4-OHE1, 4-hydroxyestrone; 2-OHE2, 2-hydroxyestradiol; SHE, Syrian hamster embryo; DES, diethylstilbestrol; 2-OHE1, 2-hydroxyestrone; DMSO, dimethyl sulfoxide; B[a]P, benzo[a]pyrene; CFE, colony-forming efficiency

Journal Article.  4519 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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