Hormonal carcinogenesis: separation of estrogenicity from carcinogenicity.
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.
D000818:Animals; D006224:Cricetinae; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects; D013737:Testis / Q000187:drug effects
D004967:Estrogens; D011960:Receptors, Estrogen; C037475:2-fluoroestradiol; D004958:Estradiol