Immunobiology and Therapeutic Manipulation of Heterotransplanted Nb Rat Prostate Adenocarcinoma Into Congenitally Athymic (Nude) Mice. I. Hormone Dependency and Histopathology2

Abstract
Nb rat prostate adenocarcinomas, induced previously by the administration of testosterone and estrogen implants, were serially studied as heterotransplants in congenitally athymic (nude) mice. Because such a tumor model is similar to human prostate adenocarcinoma, it provides a versatile system to study the biology of Nb rat prostate tumors. Eight Nb rat tumors (androgen-dependent tumors 2 Pr-125, 2 Pr-128, and 2 Pr-129-D-11A; estrogen-dependent tumors 52 Pr-16 and 52 Pr-14B; and autonomous tumors 13 Pr-12, 102 Pr-22, and Pr-90) were serially transplanted into the nude mouse. The latency period and histology remained stable in 12 generations. Moreover, the hormone characteristics of the various tumors remained stable through 12 transplant generations. The hormone dependency pattern as described in the Nb rat remained stable when the tumor was transplanted into congenitally athymic (nude) mice. Despite the deficiency of cell-mediated immunity in the nude mouse, the rate-limiting step for successful transplantation appeared to be the hormone status of the host. Such a tumor-hormone interaction may be critical in the ability or failure to transplant specific human tumors into the nude mouse. The Nb rat prostate adenocarcinoma 13 Pr-12 was heterotransplanted, to congenitally athymic (nude) mice for the evaluation of chemotherapeutic responses. This prostate tumor was uninfluenced by hormone manipulation. The chemotherapeutic effectiveness of 5-fluorouracil, cyclophosphamide, adriamycin, and methotrexate was statistically significant, P<0.OO03. This combination of animal model systems proved useful in the evaluation of chemotherapeutic agents heretofore having limited use by urologic oncologists.