Induction of Tumors in Rats With Procarbazine Hydrochloride

Summary

Single and repeated administration of procarbazine hydrochloride [N-isopropyl-α-2-(methylhydrazino)-p-toluamide, hydrochloride] by oral or intraperitoneal route induced tumors in Osborne-Mendel and Fischer rats. All the rats were less than 1 year old at death. In Osborne-Mendel rats, 90–100% of females and 70% of males developed mammary adenocarcinomas in a median latent period of 13–19 and 27 weeks, respectively, 40% of males developed hemangioendotheliomas and hemangiomas of the spleen, and several rats developed pulmonary tumors. Carcinoma of the duodenum and the jejunum, hemangioendothelioma of the kidney, uterus, and liver, leukemia, fibrosarcoma of the oral submucosa, and subcutaneous rhabdomyosarcoma each were found in one animal only. In Fischer rats, 20–60% of the females and none of the males developed mammary tumors (median latent period in females, 34–43 weeks), 40% of the females and 30% of the males developed tumors of the kidney, 10% of the females developed tumors of the uterus, 15% of the females and 30% of the males developed squamous cell carcinoma of the ceruminous and of the sebaceous glands, and a few animals developed pulmonary tumors. Leiomyosarcoma of the jejunum, ganglioneuroma of the adrenal gland, lymphosarcoma, reticulum cell sarcoma of lymph node, retroperitoneal rhabdomyosarcoma, and a subcutaneous fibrosarcoma each were found in one rat.