Induction of Hepatic Cell Carcinomas in Monkeys With N-Nitrosodiethylamine2

Abstract

Hepatic cell carcinomas were induced within 27 months (earliest tumor, 14 months; median time to tumor formation, 23 months) in 5 of 11 macaques and 1 of 4 cebus monkeys given N-nitrosodiethylamine (DENA) orally, and in 2 cercopithicus monkeys given the compound intraperitoneally. The hepatocarcinomas were multicentric, and one monkey had metastases in the lungs and the pancreatic and biliary lymph nodes. The most frequently observed prodromal change in the livers of monkeys given DENA was toxic hepatitis, characterized by sequential degeneration, transformation, and proliferation of hepatic cells. The macaques received the first dose of DENA as newborns, the cebus as adults, and the cercopithicus monkeys at the age of 6 months. The cumulative oral dosage ranged from 6 to 24 g per monkey, while the cumulative intraperitoneal dose was about 2 g per monkey. Intermittent administration of DENA (oral or intraperitoneal) was less toxic than continuous dosage. Hemograms were taken at intervals over a 2-year period on the macaques that had received DENA orally beginning at birth, and the data do not indicate any hematological changes due to treatment.