Susceptibility of nonhuman primates to carcinogens of human relevance

Abstract

Nonhuman primates are a valuable experimental model for the evaluation of human carcinogenic risk but have not been widely used for various reasons, such as high cost and lack of availability. The present review discusses the findings from a long-term carcinogenesis study in nonhuman primates that was carried out under contract by the National Cancer Institute from 1961 to 1997. Among the classes of compounds investigated were model rodent carcinogens, food additives, food and environmental contaminants, heterocyclic amines, N-nitroso compounds, and antineoplastic and immunosuppressives. Of the model rodent carcinogens tested, only urethane was carcinogenic in monkeys. Long-term administration of saccharin or cyclamate did not result in toxicity or carcinogenicity in nonhuman primates, which is commonly seen in rodent models. Similar to rodent models and suspected in the human population, the fungal toxins, aflatoxin B1 and sterimatocystin, induced malignant liver tumors in monkeys. Relatively few animals administered DDT developed malignant tumors, however, hepatic and CNS toxicity was commonly observed. Hepatocellular carcinoma developed in a majority of monkeys administered the heterocyclic amine, IQ but not the structurally similar MeIQx. Resultant toxicity and carcinogenicity from N-nitroso compounds was variable. While diethylnitrosamine proved to be the most potent hepatocarcinogen tested, no malignant tumors were seen in animals administered N-methyl-N-nitro-N-nitrosoquanidine. Susceptibility of nonhuman primates to chemotherapeutic agents was also variable. Only procarbazine and N-methyl-N-nitrosourea were highly carcinogenic, whereas few tumors were seen as a result of cyclophosphamide, Adriamycin, melphalan, or azathioprine.