Prostate cancer induction in autoimmune rats and modulation of T cell apoptosis

In this study we present an experimental model of prostate gland cancer ind uced by long term hormonal treatment with testosterone in combination with a chemical carcinogenic agent in male Wistar rats with autoimmune prostatit is (AIP). This system is particularly attractive in order to study the fact ors involved in the transition from a non-invasive to an invasive carcinoma , decisive in the risk of human cancer. At first, autoimmune prostatitis was induced by immunization in 3 months-ol d male Wistar rats with autologous accessory glands. Then, rats were treate d with continuous intradermal implants of testosterone propionate (TP) and with single doses of the chemical carcinogen 7, 12 dimethylbenz (alpha) ant hracene (DMBA) by intraperitoneal injection. Histopathological studies of t he prostate gland revealed the presence of pre-malignant lesions, particula rly the so-called prostatic intraepithelial neoplasm (PIN) in 50% of animal s. Moreover, we observed the development of carcinomas in 50% of treated-an imals, which could be histologically discriminated in adenocarcinomas, carc inoma of epidermal origin and undifferentiated carcinoma. In autoimmune rat s which did not receive any other treatment, exposure to autoantigens gave rise to an atypical hyperplasia of the prostatic gland which could be attri buted to the hyperactive state of the gland. Control groups constituted by autoimmune rats treated with TP or DMBA, and normal rats which were exposed to TP and/ or DMBA evidenced the presence of PINs at different degrees, bu t did not develop carcinomas. Moreover, serum acid phosphatase significantl y increased as treatment was accomplished, reaching its maximum levels in a nimals with carcinoma, in which DNA content, determined by image cytometry, showed to be aneuploid. Finally, we provided biochemical and cytofluoromet rical evidence of the induction of apoptosis of spleen T cells in carcinoma -bearing hosts, and to a lesser extent in animals with PIN, but not in auto immune or normal controls, which could represent an alternative molecular m echanism for explaining host immunosuppression triggered by tumors.