This long-term project continues to evaluate the potential carcinogenic effects of a multitude of substances in nonhuman primates. These include nitroso-compounds, antineoplastic and immunosuppressive agents, 'classical' rodent carcinogens, food additives, food components, and environmental contaminants. The most recent compounds introduced into the colony include the heterocyclic amines, 2-amino-3-methyl-3H-imidazo[4,5A]quinoline (IQ), 2-amino-3,8-dimethyl [4,5-f] quinoxaline (MeIQx) and 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which are potent mutagens found in cooked meat. Of a group of 20 monkeys which have received 20 mg/kg of IQ since 1985 nine are dead with primary hepatocellular carcinoma (HCC) and two are alive with HCC. Two of the monkeys receiving 10 mg/kg of IQ have died with HCC, and two are alive with HCC. DNA IQ-adducts have been found in peripheral blood cells in a number of the IQ monkeys. The MeIQx which was started 1/2 years ago has no yet revealed any liver abnormalities, and no DNA-adduct levels were found in peripheral blood cells. Monkeys sacrificed after nine doses of PhIP administration were shown to have high DNA-adduct levels in the heart and liver. Twenty monkeys have been assigned to chronic PhIP administration (20 mg/kg), three of which have already started. Concerning the other compounds used in the program the most interesting finding was a metastatic HCC diagnosed in a monkey which had received DDT for 19 years.
NIH ExPorter
NIH ExPorter