Primary liver cancer and oesophageal basal cell hyperplasia in rats caused by Fusarium moniliforme.

Fusarium moniliforme Sheldon is one of the most prevalent fungi associated with maize throughout the world. A correlation has been found between the incidence of F. moniliforme in home-grown maize and the human oesophageal cancer rate in Transkei, southern Africa. Culture material on maize of F. moniliforme strain MRC 826, isolated from maize in a high-risk area for oesophageal cancer in Transkei, was either freeze-dried or oven-dried and fed to groups of 20 inbred male BD IX rats on a life-long basis. At a dietary level of 8%, both types of culture material were hepatotoxic and caused 100% mortality. Hepatic lesions in rats that died were characterized by cirrhosis, nodular hyperplasia and bile-duct proliferation. At a dietary level of 4% for 286 days followed by 2% for the remainder of the experiment, both types of culture material were hepatocarcinogenic and caused hepatocellular carcinoma in 80% and ductular carcinoma of the liver in 63% of the rats surviving more than 450 days. Only one of 30 such rats did not have a primary hepatic carcinoma. No hepatocellular or ductular carcinomas occurred in the controls. Hepatocellular carcinomas in the experimental rats invariably developed in severely cirrhotic livers showing nodular hyperplasia. Adenofibrosis also developed concurrently with hepatocellular carcinoma. A higher incidence of basal cell hyperplasia occurred in the oesophageal epithelia of rats fed freeze-dried than in those fed oven-dried material. The chemical nature of the hepatotoxic and hepatocarcinogenic mycotoxin(s) produced by F. moniliforme is unknown.