TUMOR-INCIDENCE IN A CHEMICAL CARCINOGENESIS STUDY OF NONHUMAN-PRIMATES

This report covers a 32-year period of an ongoing chemical carcinogene sis study in nonhuman primates, which was initiated by the National Ca ncer Institute in 1961. Autopsy records of 373 breeders and normal con trols showed very law incidence of spontaneous malignant tumors in cyn omolgus (1.5%) and rhesus (2.8%) monkeys, but considerably higher inci dence in African green monkeys (8%). A large number of substances incl uding a variety of food additives, food components, environmental cont aminants, N-nitroso compounds, ''classical'' rodent carcinogens, antin eoplastic agents, and immunosuppressive agents have been evaluated for long-term carcinogenic activity. Food components tested which are pro bably most relevant to human exposure are the artificial sweeteners, c yclamate and saccharin. After 22 years of continuous dosing, neither c yclamate nor saccharin have shown any evidence of carcinogenic effects . Similarly, the tumorigenic potential of arsenic and DDT was negligib le after dosing for 15-22 years. In contrast, the fungal food contamin ants, aflatoxin B-1 (AFB(1)) and sterigmatocystin (SMT), were found to be potent hepatocarcinogens. AFB, also induced adenocarcinomas of the pancreas, osteosarcomas, and other tumors. Also, the aglycone of cyca sin, MAM acetate, induced a variety of tumors, but primarily hepatocel lular and renal cell carcinomas. The compounds most recently introduce d into the colony include three heterocyclic amines present in cooked meat. One of these compounds, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has proven to be one of the most potent hepatocarcinogens in the history of the monkey project, inducing malignant liver tumors in 65% of animals over a 7-year period of exposure. Of the classical rodent c arcinogens studied, urethane was the only one which produced malignant tumors in the monkeys. Conversely, all except two of the N-nitroso co mpounds were carcinogenic. Diethylnitrosamine (DENA) was the most pote nt and predictable hepatocarcinogen in cynomolgus, rhesus, and African green monkeys. However, when administered intraperitoneally to galago s (a prosimian), DENA induced primarily mucoepidermoid carcinoma of th e nasal cavity. N-Methyl-N-nitrosourea (MNU) was the only carcinogen p ersistently producing tumors in the digestive tract, mostly squamous c ell carcinomas of the esophagus. Among the antineoplastic and immunosu ppressive agents, procarbazine (MIH) was the only unequivocal carcinog en, with a 33% tumor incidence, causing acute nonlymphocytic leukemia in most of the cases. (C) 1994 Academic Press, Inc.