Model of prostate cancerogenesis

Bespalov V.G., Murazov Ya.G., Kuzhanov A.A., Panchenko A.V., Chepik O.F.

Two new modifications of a combined two-phasic model of the prostate carcinogenesis are developed. Experiments were carried out in 86 Wistar male rats. At the first variant the rats were subjected to surgical castration, single intraperitoneal administration of the prolonged testosterone drug Omnadren at a dose of 833 mg/kg of body weight, and single intravenous injection of a carcinogen methylnitrosourea at a dose of 833 mg/kg of body weight and then the rats were administered intraperitoneal injection of omnadren at promoting doses of 16.7 mg/kg of body weight within 60 days 2 times a week and within 42 weeks once a week. As a result the rats were simultaneously developed with high incidence and multiplicity the prostate precancerous changes such as high-grade and lowgrade prostatic intraepithelial neoplasia of flat, tufting, micropapillary, and cribriform patterns and also the localized, locally advanced, and metastatic prostate cancer with high Gleason grade. The overall incidences of the prostatic intraepithelial neoplasia and prostate cancer were 76.5% and 64.7%, correspondingly. In the second variant the rats were subjected to temporary pharmacological with Ciproterone acetate and then were administered Omnadren and methylnitrosourea as well as in the first variant but the promotion by Omnadren spent only within 60 days. As a result the rats were developed with high incidence and multiplicity only prostatic intraepithelial neoplasia with the 75% overall incidence. The developed models are recommended for preclinical testing of preparations potentially useful for the primary and secondary prostate cancer chemoprevention.

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