A single i.p. injection of 1 mg urethan per g body weight was given to 7- and 21-day-old male and female C3Hf mice. This treatment had previously been shown to induce hepatomas in 60% of females and 95% of males treated at the age of 7 days and in 5% of females and 65% of males treated at the age of 21 days. The sequence of ultrastructural nucleolar alterations in hepatic cells was studied. No sex-dependent differences in the lesions were found. In 7-day-old animals, microspherules were found either within the meshes of the nucleolar network or at the periphery of the nucleolus, 4 and 12 hr after dosing. At 24 hr, segregation of granular and fibrillar nucleolar components (nucleolar capping) was demonstrated. By 72 hr, restoration of normal nucleolar structure was observed. Twenty weeks later, hyperplastic nodules were macroscopically evident. In both normal and hyperplastic tissue, disaggregation of nucleolus-associated chromatin, and, more rarely, ring-shaped nucleoli was observed. Mice treated at 21 days of age did not develop nucleolar lesions, but disaggregation of the nucleolus-associated chromatin was demonstrated at 4, 12, 24, and 72 hr and at 20 weeks after the treatment. In conclusion, this research has demonstrated that a carcinogenic dose of urethan produces nucleolar and chromatinic changes in the mouse hepatocytes.

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