The ability of four catechol estrogens of 17 beta-estradiol and estrone toinduce DNA adducts in Syrian hamster embryo fibroblasts

Catechol estrogens are considered critical intermediates in estrogen-induce d carcinogenesis. We demonstrated previously that 17 beta -estradiol (E-2), estrone (E-1) and four of their catechol estrogens, 2- and 4-hydroxyestrad iols (2- and 4-OHE2,), and 2- and 4-hydroxyestrones (2- and 4-OHE1) induce morphological transformation in Syrian hamster embryo (SHE) fibroblasts, an d the transforming abilities vary as follows: 4-OHE1 > 2-OHE1 > 4-OHE2 > 2- OHE2 greater than or equal to E-2, E-1. To examine the involvement of catec hol estrogens in the initiation of hormonal carcinogenesis, we studied the ability of E-2, E-1 and their catechol estrogens to induce DNA adducts in S HE cells by using a P-32-post- labeling assay. DNA adducts were detected in cells treated with each of all the catechol estrogens at concentrations of 10 mug/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-OHE 2 produced one major and one minor adduct, and the two adducts formed by ea ch catechol estrogen exhibited identical mobilities on the chromatograms. N either E-2 nor E-1 at concentrations up to 30 mug/ml induced DNA adducts. T he abilities of the estrogens to induce DNA adducts were ranked as follows: 4-OHE1, > 2-OHE1 > 4-OHE2 > 2-OHE2 >> E-2, E-1, 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 dec reased by co-treatment of cells with the antioxidant L-ascorbic acid. The r esults indicate the possible involvement of oxidative metabolites of catech ol estrogens of E-2 and E-1 in the initiation of endogenous estrogen-induce d carcinogenesis.