Ethanol-induced changes in hepatic chromatin and nonhistone nuclear protein composition in the rat.

Excessive ethanol consumption has been shown to affect hepatic nucleic acid and protein synthesis. This study was undertaken to identify the changes in hepatic chromatin and nonhistone nuclear proteins as a consequence of chronic ethanol treatment, because these changes could be contributory to alcoholic cirrhosis. Chromatin conformation was monitored by circular dichroism spectrophotometry. The chromatin from alcoholic rat liver showed decreased molar ellipticity (theta). This change in chromatin conformation influences chromatin functions such as replication and transcription through the regulatory pool of nonhistone nuclear (NHN) proteins. The NHN proteins were analysed by ultrasensitive two-dimensional gel electrophoresis. Specific changes in nuclear proteins were documented in the liver of chronic alcohol-fed rats. This study shows chronic ethanol-induced changes in chromatin conformation and nuclear proteins, which might be critical in the mechanism of alcoholic cirrhosis.