Prevention and treatment of experimental prostate cancer in Lobund-Wistar rats. I. Effects of estradiol, dihydrotestosterone, and castration.
The Lobund-Wistar (L-W) rat is unique in its susceptibility to spontaneous and induced metastasizing prostate adenocarcinomas (PAs). A single IV inoculation of methylnitrosourea (MNU) produced PAs in 20% of L-W rats in 12 months. The combination of MNU plus two to seven slow-release implants of testosterone propionate (TP) induced PAs in 50-90% of rats respectively in an average of 11.5 months. The induction of PAs was prevented by early treatments of rats at risk with estradiol and less so with dihydrotestosterone (DHT). However, on a technical basis, the results were not significant. Treatments of MNU-inoculated rats with estradiol, with DHT, or by castration, at intermediate points in the projected latency time of tumor development, reduced significantly the incidences of PA development. Rats in which overt PAs had already developed in response to 12 months of exposure to implants of TP did not respond to treatment by estradiol, DHT, or castration. Thus there are early stage(s) in induced prostate tumorigenesis in L-W rats that are sensitive to modulating agents.
Pollard
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Lobund Laboratory, University of Notre Dame, Indiana 46556.
Luckert
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Snyder
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D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D000818:Animals; D013196:Dihydrotestosterone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004958:Estradiol / Q000627:therapeutic use*; D005856:Germ-Free Life; D008297:Male; D009367:Neoplasm Staging; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D013196:Dihydrotestosterone; D004958:Estradiol