Hormonal carcinogenesis: separation of estrogenicity from carcinogenicity.

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.

• Authors: J G Liehr, G M Stancel, L P Chorich, G R Bousfield, A A Ulubelen
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 59 Issue 2 Pg. 173-84 (Sep 1986) ISSN: 0009-2797 [Print] Ireland
• PMID: 3769051 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Estrogens
• Receptors, Estrogen
• 2-fluoroestradiol
• Estradiol

Topics

• Animals
• Cricetinae
• Estradiol (analogs & derivatives, pharmacology)
• Estrogens (metabolism, pharmacology, toxicity)
• Female
• Kidney Neoplasms (chemically induced)
• Male
• Mesocricetus
• Organ Size (drug effects)
• Pituitary Gland (drug effects)
• Rats
• Receptors, Estrogen (drug effects)
• Testis (drug effects)