Abstract
Histological and flow cytometry (FCM) analyses were performed of carcinogenesis of rat prostate cancer induced with N-Nitroso-N-methylurea (NMU). Ten-week-old rats were inoculated intravenously (i. v.) with twice injections of NMU (30mg/kg body weight) and then, divided into 3 groups; Group 1: the rats were injected subcutaneously with LH-RH analogue (100μg/kg b. w.) every 4 weeks. Group 2: the rats were injected subcutaneously with testosterone enanthate (10mg/body) every 2 weeks and Group 3: the rats were untreated to serve as controls. We further divided Groups 1 and 2 into (+) and (-) subgroups at 34 weeks after initial injection. Group 1 (+) or 2 (+) rats were continuously given the drug and in Group 1 (-) or 2 (-) rats the drug was suspended. At 44 or 53 weeks after initial injection, we removed the prostate and seminal vesicles of all rats and performed histological and FCM analyses of them. Histological analysis of rat prostates revealed hyperplasia in each group, and both Groups 2 (+) and 2 (-) showed an incidence as high as 87.5%. Atypical hyperplasia was sometimes observed in each group and its incidence was not significantly different between any 2 groups. At 51 weeks after initial injection, a macroscopic adenocarcinoma (weighing about 11g) was found in the prostate of a dead rat of Group 2 (+). Histological analysis of rat seminal vesicles revealed hyperplasia in each group, in particular in Groups 2 (+) and 2 (-). In these groups all rats showed hyperplasia. At 53 weeks after initial injection, two rats of Group 2 (+) showed atypical hyperplasia and another rat of Group 2 (+) showed a macroscopic adenocarcinoma. In FCM analyses of the prostates and the seminal vesicles, aneuploid pattern was observed in each group with insignificant difference between any 2 groups. There was no meaningful correlation between histological analyses and FCM analyses of the prostates and the seminal vesicles.
