Role of Estrogen in Androgen-Induced Prostate Carcinogenesis in NBL Rats.

Androgens are thought to cause prostate cancer, but the underlying mechanisms are unclear. Data from animal studies suggest that for androgens to cause prostate cancer, they must be aromatized to estrogen and act in concert with estrogen metabolites. We tested the hypothesis that androgen-receptor and estrogen receptor-mediated effects of androgen and estrogen are necessary, as well as genotoxicity of estrogen metabolites.

Specific binding of 4-hydroxyestradiol to mouse uterine protein: evidence of a physiological role for 4-hydroxyestradiol.

There are several indications of a possible physiological role for 4-hydroxyestradiol (4-OHE(2)) in hormone-responsive tissues. To examine a hormonal activity of 4-OHE(2), we have studied the binding of (3)H-labeled 4-OHE(2) to mouse uterine cytosolic protein. In uteri of 3-week-old mice, total binding was 319.

Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development.

Oestrogens, including the natural hormones oestrone and oestradiol, induce various tumours in laboratory animals and have been recognized to be carcinogens in humans, raising the risk for breast and uterine cancer. As part of the search for the mechanism of hormone-induced carcinogenesis, various types of DNA damage have been detected which have been induced by oestrogens in cell-free systems, in cells in culture, or in vivo. Nevertheless, oestrogens have been postulated to act only as promoters of mammary carcinogenesis by receptor-mediated growth stimulation without consideration of their genotoxicity because these hormones failed to induce mutations in commonly used assays.

Role of estrogen in alcohol promotion of breast cancer and prolactinomas.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Dipak K. Sarkar.

Role of iron in estrogen-induced cancer.

Redox cycling of catecholestrogen metabolites between quinone and catechol forms is a mechanism of generating potentially mutagenic oxygen radicals in estrogen-induced carcinogenesis. Consistent with this concept, multiple forms of oxygen radical-generated DNA damage are induced by estrogen in cell-free systems, in cells in culture and in rodents prone to estrogen-induced cancer. Metal ions, specifically iron, are necessary for the production of hydroxy radicals.