During the thirty years of the ongoing monkey carcinogenesis project, the carcinogenic potentia of forty-four compounds has been tested. These include antineoplastic and immunosuppressive agents; food additives, food components and environmental contaminants; classical rodent carcinogens; nitroso-compounds; and viruses. In 1985 a heterocyclic amine found in cooked meat, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) was introduced in the monkey colony. In a group of twenty animals receiving 10 mg/kg of IQ, three are dead with hepatocellular carcinoma and two are alive with tumor. In another group of twenty animals receiving 20 mg/kg of IQ, thirteen are dead with hepatocellular carcinoma and two are alive with tumor. Dosing of two other heterocyclic amines, 2-amino-3,8-dimethyl[4,5-f]quinoxaline (MeIQx) was started in 1987 and 2-amino-l-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) in 1990. So far, there is no evidence of tumor development in either group. DNA adducts have been measured for both IQ and PhIP in peripheral blood cells and various organs, particularly in liver and heart. Ongoing studies are focusing on metabolic activation of IQ and MeIQx in monkeys and the high cardiac adduct levels of IQ and PhIP. The possibility exists that they may cause myocardial damage unrelated to neoplasia. Several collaborative studies have been initiated this year which utilize monkey tissues from different treatment groups. These include: 1) ultrastructural and histochemical studies of myocardium from monkeys dosed with IQ; 2) histopathological study of adriamycin induced myocardial degeneration; 3) evaluation of p53 suppressor gene mutations in PCR amplified DNA from aflatoxin-induced hepatocellular carcinomas; and 4) histopathological and histochemical studies of DENA induced liver tumors and precursor lesions.
