Diethylnitrosamine (DENA) has proven to be the most potent and persistent hepatocarcinogen in the monkey carcinogenesis project with a latency period of 1-2 years when administered intraperitoneally at a dose of 40 mg/kg. Here DENA is used as a model compound to induce hepatocellular carcinoma and follow progression of the carcinogenic process. Of seven monkeys that were placed on DENA in January 1990, two died within a few months as a result of massive liver necrosis due to DENA toxicity. The five remaining animals tolerated the DENA well. Laparoscopies performed at 1-2 month intervals revealed considerable variability in the hepatic response; some were affected by DENA earlier and more severely than others. Generally, the liver became pale and tannish in color within two months of dosing. The frequent needle biopsies induced scarring of the liver capsule and shrinking of the lobes involved in both test animals and the two controls that received only the vehicle, PBS. Hyperplastic nodules were observed in some of the animals within 6-8 months. After one year the livers of two of the monkeys appeared cirrhotic and entirely replaced with nodules of varying size. One of the two animals developed intestinal hemorrhage and severe lethargy and was sacrificed after 16 months of dosing with DENA. The entire liver of this animal was riddled with nodules with intervening fibrous bands. The nature of the liver nodules is being evaluated. The two control animals that are receiving only the vehicle for DENA, i.e. PBS, have not revealed any abnormalities except for fibrous reaction and shrinking of the liver lobes due to the frequent needle biopsies.
