Abstract
Estrogens are known to induce tumors in several animal species. To understand the mechanism of hormonal carcinogenesis, estrogen-induced renal carcinoma in male Syrian hamsters was investigated using estradiol and 2-fluoroestradiol. The biological activities of the latter steroid were compared with those of the natural hormone, because of the reduced metabolic conversion of 2-fluoroestradiol to catechol estrogen metabolites. 2-Fluoroestradiol was administered to male Syrian hamsters at three times the dose (60 mg) of estradiol (20 mg, positive control) by s.c. implantation. After 7 months, 75% of the estradiol-treated hamsters had kidney tumors, while in animals exposed to 2-fluoroestradiol renal carcinoma could not be detected. The reduced tumor incidence by the fluorinated steroid is not due to a lack of estrogenic potency. In the test animals, pituitary LH concentrations matched those measured in estradiol-treated hamsters and the reduction in testes weights was comparable. Furthermore, in immature female rats, uterine wet weight increases illustrate that 2-fluoroestradiol is a potent estrogen. The observed increases in uterine weight were shown to be accompanied by increases in protein and DNA synthesis comparable to those observed in estradiol-treated animals. 2-Fluoroestradiol stimulated growth of H-301 cells in vivo. These cells are estrogen-dependent for growth and are derived from the primary hamster kidney tumor. The results indicate that hormonal activity and carcinogenicity of estrogens are separable properties.
Original language | English (US) |
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Pages (from-to) | 173-184 |
Number of pages | 12 |
Journal | Chemico-Biological Interactions |
Volume | 59 |
Issue number | C |
DOIs | |
State | Published - 1986 |
Keywords
- 17β-estradiol
- 2-F-E2
- 2-Fluoroestradiol
- 2-fluoro-17β-estradiol
- Carcinogenicity
- DES
- E-diethylstilbestrol
- E2
- Estradiol
- Estrogenicity
ASJC Scopus subject areas
- Toxicology