Effects of chronic ethanol feeding on rat hepatocytes.

Ethanol was fed at a level of 35% of total caloric intake to mature male rats for intervals of one to 38 days. Mitochondrial content of cytochrome c oxidase per mg protein was maximally depressed, to 40% of control values, after 10 days feeding. After 15 days of ethanol feeding, leucine incorporation into total hepatocyte protein, as well as into total intracellular (subcellular fractions) or extracellular (secreted) proteins was substantially inhibited. At the level of total protein, alterations in isotope ratio as a consequence of ethanol feeding were only manifest in the secreted proteins. However, when component proteins of subcellular fractions were separated by gel electrophoresis, two specific early effects of ethanol feeding on protein synthesis by the endoplasmic reticulum could be detected. Aberrant isotope ratios established that synthesis of two entities, of 20000 and 50000 apparent molecular weight, was depressed after intervals of one and five days, respectively, feeding of 10% ethanol.