An intracellular defect in protein synthesis induced by carbon tetrachloride

The morphological and certain metabolic effects of carbon tetrachloride intoxication were studied in the rat with emphasis on liver alterations. Morphological changes were investigated by histological and electron microscopical means. Functional changes were investigated using histochemical and amino acid incorporation, techniques. The liver constituents were examined chemically. Plasma volume alterations were measured using dye and homologous protein dilution techniques. The histological appearance of the liver of treated animals included cellular swelling, dispersal of the cytoplasmic basophilia, and necrosis. Electron micrographs showed an early (3 hours following carbon tetrachloride administration) and widespread dislocation of the ribonucleoprotein particles from the membranes of the rough endoplasmic reticulum, but no apparent alteration in the mitochondrial structure. Histochemical examination of two mitochondrial enzyme systems, alpha-ketoglutarate dehydrogenase and succinic dehydrogenase, revealed no alterations in activities until a later time (6 to 12 hours following carbon tetrachloride administration). ATPase showed a gross quantitative decrease in activity at 6 and 12 hours, but not earlier. There was a decreased amino acid incorporation into two liver-produced proteins, viz., albumin and fibrinogen. This decrease is not explicable on the basis of the inability of the liver to take up the amino acid, an altered dilution volume into which the amino acid or formed protein is placed, or an impaired capacity of the liver to excrete protein once formed. It is concluded that the decreased amino acid incorporation rate reflects depressed synthesis of protein by the liver. Other pathological changes in the liver, including necrosis, fatty change, and mitochondrial alterations may be dependent upon severe impairment of protein synthesis.