Twenty heterocyclic aromatic amines (HCA) have been identified in cooked meat. The possibility that these highly mutagenic HCAs are human carcinogens prompted a collaboration with Japanese scientists to test three of these agents in nonhuman primates. The HCA, 2-amino-3- methylimidazo[4,5-f]quinoline, which was first administered to the monkeys in 1985 has been shown to be a potent hepatocarcinogen and has also caused myocardial damage, which may be related to high levels of cardiac IQ DNA adducts. Dosing of the second HCA, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MeIQx) was initiated in 1987 and 2- amino-1-methylimidazo[4,5-b]pyridine was introduced in 1990. Monkeys chronically dosed with MeIQx and PhIP have not demonstrated any signs of tumor development or toxicity. New studies have begun to evaluate the effect of high fat diet on the carcinogenic potential of IQ. One of the monkeys in this group, which died suddenly, had evidence of liver toxicity. This raises an interesting question of whether a high fat diet precipitates hepatotoxic effects of IQ. Monkeys which have been chronically dosed with cyclamate and saccharin since 1970, and DDT monkeys that were dosed from 1970 until 1981, were euthanized and autopsied recently. The few cases of malignant tumors that emerged in these groups after more than 20 years, cast a doubt on a possible role of cyclamate, saccharin, and DDT in the tumor induction. Studies on testes, urine and plasma from the cyclamate monkeys demonstrated that cyclamate was converted to cyclohexylamine at a comparable rate to that observed in rodents. There was some indication of testicular atrophy which is presently being evaluated. Thalidomide has been shown to inhibit angiogenesis in a rabbit cornea. A group of adult monkeys has been assigned to a study to examine if thalidomide can inhibit neo-vascularization of diethylnitrosamine-induced hepatocellular carcinomas.
