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Sequential hepatic changes during sterigmatocystin-induced carcinogenesis in the rat.

The effect of protein deficiency on the hepatotoxicity and carcinogenicity of sterigmatocystin was studied in rats. Sterigmatocystin, 500 ppm/day, fed in a regular diet induced marked toxic effects and there was a high incidence of hepatocellular carcinoma and hyperplastic nodules. The same dosage fed in a protein-deficient diet produced toxic signs followed by a high incidence of death within 27 weeks. Surviving animals showed dysplastic liver cell changes but no tumors were noted. The incidence of hepatocellular carcinoma was 87% in rats receiving 15 ppm of the substance per day for 200 days in a protein-deficient diet. Sequential histologic and histochemical studies revealed that hyperplastic and preneoplastic liver lesions appeared at 28--32 weeks after inseption of the sterigmatocystin-supplemented diet. No cirrhotic changes and only transient fibrosis were noted. The morphogenesis of the sterigmatocystin-induced lesions was compared with that of aflatoxin B1-induced lesions.