Development of androgen-independent carcinomas from androgen-dependent preneoplastic lesions in the male accessory sex organs of rats treated with 3,2 '-dimethyl-4-aminobiphenyl and testosterone propionate

Two kinds of cancer can be induced in rat male accessory sex organs, one a non-invasive carcinoma arising in the ventral lobe and the other an invasiv e lesion which develops in the dorsolateral and anterior lobe as well as th e seminal vesicles, In the present study, one group of male rats were given biweekly s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) for 20 we eks for induction of non-invasive carcinomas and the other group received D MAB with 40-week testosterone propionate for induction of invasive carcinom as. Half of the animals in each group were then subjected to bilateral orch iectomy at week 41 to remove testicular androgen, in order to examine the a ndrogen dependence of both types of carcinomas as well as precancerous lesi ons. Animals were killed at weeks 41, 46 and 60, All parts of the prostate complex showed involution and significant weight reduction after castration , with a complete disappearance of atypical hyperplasias and carcinomas of the ventral prostate. However in spite of suppression of development of aty pical hyperplasias in the anterior prostate and seminal vesicles, the incid ence of invasive carcinomas was not changed. Normal epithelial cells and at ypical hyperplasias of all parts of the prostate and seminal vesicles and c arcinomas of the ventral prostate were immunohistochemically positive for n uclear androgen receptor, while invasive carcinomas that developed in eithe r castrated or noncastrated animals were negative. These findings suggest t hat in the central prostate, both precancerous and cancerous lesions are an drogen-dependent, but in the anterior and seminal vesicles, cancerous lesio ns (invasive carcinomas) are androgen-independent while precancerous lesion s are hormone-dependent.