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An analysis of nuclear and chromatin proteins in rat livers exhibiting hyperplastic growth induced by chemical carcinogens.

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Hyperplastic growth and expression of gamma-glutamyl transpeptidase were induced in adult rat hepatocytes using a model of chemical hepatocarcinogenesis. The hyperplastic response was maximal at 10 weeks after initiation of the model, at which time some 20-25% of the cross-sectional area of liver sections showed hepatocyte expression of gamma-glutamyl transpeptidase. The altered growth patterns appeared to be independent of carcinoma development since at 12 months after initiation only one of 10 animals showed evidence of hepatocellular carcinoma. A 43,000 dalton protein of isoelectric point 6.9 was solubilized by DNASE I from nuclei derived from livers at 10 weeks after initiation of the regime. This protein was scarcely detectable in the nuclei of control livers or in control and treated livers at other times after initiation of the regime. These observations suggest that alterations to a prominent nonhistone protein associated with the transcriptionally active fraction of chromatin occurred during hyperplastic growth of hepatocytes induced by chemical carcinogens.

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