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Influence of Phenobarbital on Microspherule Production by Urethan in Mouse Hepatocyte Nucleoli

Division of Experimental Oncology A, Istituto Nazionale per to Studio e la Cura dei Tumori, Via G. Venezian 1, 20133 Milan, Italy

Four-day-old C3Hf mice received one daily i.p. injection of phenobarbital (30 mg/kg body weight) in 0.9% NaCl solution or of 0.9% NaCl solution alone for 3 days. On the fourth day the mice were treated with a single i.p. injection of urethan (1 mg/g body weight) in 0.9% NaCl solution or of 0.9% NaCl solution alone. The mice were killed 10 hr after the last injection, and the liver tissue was studied by electron microscopy.

Aggregates of an essentially proteinaceous fibrillar material were observed in the hepatocyte nucleoli of 0.9% NaCl solution-treated control mice. After treatment with phenobarbital alone, which induced the typical proliferation of hepatocyte smooth endoplasmic reticulum, the mean number of fibrillar aggregates per nucleolus was 19% lower than that of the controls.

After treatment with urethan alone, microspherules with a similar structure, but which were somewhat larger and denser than control fibrillar aggregates, were observed. The mean number of microspherules plus fibrillar aggregates per nucleolus was 91% higher than the mean number of control fibrillar aggregates. After treatment with phenobarbital followed by treatment with urethan, the mean number of microspherules plus fibrillar aggregates per nucleolus was 36% lower than that after treatment with urethan alone. This inhibition of urethan action is probably related to drug-metabolizing enzyme induction by phenobarbital.

Received 5/ 9/77. Accepted 9/12/77.