During the past ten years the only new chemicals introduced in the monkey colony were heterocyclic amines found in cooked meat, i.e. 2-amino-3- methylimidazo-[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (8-MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Dosing of forty monkeys with IQ was started in 1985. Eighty percent of the twenty animals dosed 20 mg/kg orally five times per week (average latent period 42.4 m), and 40% of the animals dosed with 10 mg/kg (average latent period 58.5 m) have developed hepatocellular or mixed hepatocellular and cholangiocarcinomas. So far, there is no evidence of tumor development in the monkeys dosed with 8-MeIQx (since 1987) and PhIP (since 1990). A histopathological study of hearts from immediate autopsies of monkeys chronically dosed with IQ revealed focal myocyte degeneration and mitochondrial abnormalities. To further examine the possibility of IQ-induced myocardial damage, the effect of IQ and its metabolites on cardiac myocytes is being assessed in a cell culture system. Studies of IQ metabolism in monkeys suggested that N-hydroxy- lation of IQ plays a role in the initiation of the hepatocarcinogenic process. Other ongoing studies include: 1) evaluation of p53 suppressor gene mutations in carcinogenically-induced tumors, using PCR amplified DNA; 2) examination of IQ-induced tumors for mutations in oncogenes and suppressor genes; 3) formation and repair of DNA adducts in tissues and white blood cells in monkeys dosed with IQ and PhIP, as well as DNA repair in specific genes; 4) accelerator mass spectrometric studies on the metabolism of hamburger equivalent doses of PhIP.
