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Relationship between Nucleolar Microspherule Formation by Urethan and Inhibition of RNA and Protein Synthesis

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

Liver tissues of suckling C3Hf mice treated with urethan, a carcinogen and inhibitor of RNA synthesis, and with cycloheximide, an inhibitor of protein synthesis, were studied by electron microscopy and by light microscope radioautography.

At 4 and 12 hr after treatment with a single dose of urethan (1 mg/g body weight), [³H]uridine incorporation in hepatocyte nuclei was 38 and 9% lower than in controls and became 32% higher at 24 hr. Nucleolar microspherules were found 1.5 and 4 hr after the treatment, increased considerably in number at 10 and 12 hr, and decreased at 24 hr. These results suggest an inverse relationship between RNA synthesis and formation of microspherules.

Cycloheximide alone (3 mg/kg body weight) produced microspherules, whereas in combination with a dose of 1 or 2 mg of urethan per g body weight it partially prevented or potentiated, respectively, the microspherule production.

Received 10/23/75. Accepted 3/30/76.