The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17β-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16α-hydroxyestradiol, and 4-hydroxyestrone
| Autor: | Rosa I. Sanchez, Sara Antonia Li, F. C. Kauffman, P E Thomas, Valerie K. Turan, J J Li, M A Gallo, A H Conney, S. Mesia-Vela, K R Reuhl |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Hydroxyestrones Endocrinology Diabetes and Metabolism chemistry.chemical_compound Endocrinology In vivo Internal medicine medicine Animals 4-Hydroxyestradiol 4-Hydroxyestrone Carcinogen Drug Implants Mammary tumor Dose-Response Relationship Drug Estradiol Estriol Cholesterol Carcinoma Ductal Breast Mammary Neoplasms Experimental Estrogens Estrogens Catechol Rats Rats Inbred ACI Dose–response relationship chemistry Microsome Female Carcinoma in Situ |
| Zdroj: | Journal of Endocrinology. 183:91-99 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1677/joe.1.05802 |
| Popis: | Several investigators have suggested that certain hydroxylated metabolites of 17β-estradiol (E2) are the proximate carcinogens that induce mammary carcinomas in estrogen-sensitive rodent models. The studies reported here were designed to examine the carcinogenic potential of different levels of E2 and the effects of genotoxic metabolites of E2 in an in vivo model sensitive to E2-induced mammary cancer. The potential induction of mammary tumors was determined in female ACI rats subcutaneously implanted with cholesterol pellets containing E2 (1, 2, or 3 mg), or 2-hydroxyestradiol (2-OH E2), 4-hydroxyestradiol (4-OH E2), 16α-hydroxyestradiol (16α-OH E2), or 4-hydoxyestrone (4-OH E1) (equimolar to 2 mg E2). Treatment with 1, 2, or 3 mg E2 resulted in the first appearance of a mammary tumor between 12 and 17 weeks, and a 50% incidence of mammary tumors was observed at 36, 19, and 18 weeks respectively. The final cumulative mammary tumor incidence in rats treated with 1, 2, or 3 mg E2 for 36 weeks was 50%, 73%, and 100% respectively. Treatment of rats with pellets containing 2-OH E2, 4-OH E2, 16α-OH E2, or 4-OH E1 did not induce any detectable mammary tumors. The serum levels of E2 in rats treated with a 1 or 3 mg E2 pellet for 12 weeks was increased 2- to 6-fold above control values (~30 pg/ml). Treatment of rats with E2 enhanced the hepatic microsomal metabolism of E2 to E1, but did not influence the 2- or 4-hydroxylation of E2. In summary, we observed a dose-dependent induction of mammary tumors in female ACI rats treated continuously with E2; however, under these conditions 2-OH E2, 4-OH E2, 16α-OH E2, and 4-OH E1 were inactive in inducing mammary tumors. |
| Databáze: | OpenAIRE |
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