INDUCTION OF OSTEOGENIC SARCOMAS AND TUMORS OF THE HEPATOBILIARY SYSTEM IN NONHUMAN-PRIMATES WITH AFLATOXIN B-1

Abstract

The carcinogenicity of aflatoxin B1 (AFB1) has been under evaluation in nonhuman primates for the past 13 yr. A total of 47 old Old World monkeys, chiefly rhesus and cynomolgus, have received AFB1 i.p. (0.125-0.25 mg/kg) and/or p.o. [orally] (0.1 to 0.8 mg/kg) for 2 mo. or longer, and 12 are currently alive and without evidence of tumor. Of the 35 monkeys necropsied to date, 13 (37%) developed 1 or more malignant neoplasms, yielding an overall tumor incidence of 28%. Five of the neoplasms were primary liver tumors (2 hepatocellular carcinomas and 3 hemangioendothelial sarcomas) and 2 cases of osteogenic sarcoma were found. Other tumors diagnosed were 6 carcinomas of the gall bladder or bile duct, 3 tumors of the pancreas or its ducts, and 1 papillary Grade 1 carcinoma of the urinary bladder. The tumors developed in animals receiving an average total AFB1 dose of 709 mg (range, 99-1354 mg) for an average of 114 months (range, 47-147 months). Of the 22 necropsied monkeys, 15 (68%) without tumor showed histological evidence of liver damage, including toxic hepatitis, cirrhosis and hyperplastic liver nodules. These animals had received an average total AFB1 dose of 363 mg (range, 0.35-1368 mg) for an average of 55 mo. (range, 2-141 mo.). AFB1 is apparently a potent hepatotoxin and carcinogen in nonhuman primates. Humans exposed to this substance may be at risk of developing cancer.