Chronic toxicity and hepatocarcinogenicity of (+) rugulosin, an anthraquinoid mycotoxin from penicillium species: preliminary surveys in mice.

(+) Rugulosin (RUG) is bis-anthraquinoid pigment produced by fungi such as Penicillium rugulosum Thom, P. tardum and others, and its chemical structure is very close to (-) luteoskyrin, one of bis-anthraquinoid pigments of Penicillium islandicum Sopp and hepatocarcinogenic to mice and rats. This investigation was concerned with the subacute and chronic effects of RUG on hepatic injury and hepatocellular tumor induction in male mice fed purified diets for 22 days containing 1.5 mg/5 g diet/animal per day or whole feeding period containing 0.3 and 0.75 mg RUG/5 g diet/animal per day. A half of male DDD mice receiving 1.5 mg RUG for the initial 22 days of feeding died 1-3 weeks thereafter from the acute hepatic injury characterized by fatty degeneration and liver cell necrosis, and hepatocellular carcinoma developed in one out of 14 mice surviving the feeding of control diet for additional 400 days. Each one fourth of cases of male ddYS mice receiving 0.3 and 0.75 mg RUG for 500-700 days developed hyperplastic nodules of liver cells. These data suggest that RUG is possibly a weak hepatocarcinogen for male mice with a potency les than one tenth of (-) luteoskyrin.