The effect of carbon tetrachloride poisoning on subcellular metal distribution in rat liver.

The mechanism by which the ingestion of carbon tetrachloride results in distinct and reproducible histological alterations of the liver has been investigated intensively, both in &JO and in vitro (3-11). The mitochondria of liver cells are particularly vulnerable to this lipid solvent, as shown by their increased permeability (3), decreased coenzyme content (7, 8), and the loss of their ability to oxidize substrates (8) and to carry out esterifications of high energy phosphate coupled with oxidation (9). In a series of investigations on the mechanism of carbon tetrachloride poisoning in the liver of the rat, a specific and characteristic chemical lesion involving alkali metals and alkaline earths has been detected. Large increases in calcium and concomitant decreases in potassium are found reproducibly in liver mitochondria obtained from rats to which this agent was administered. Both in vivo and in titro, these compositional changes correlate with alterations of the oxidative function of mitochondria. The present paper reports on the time courses of these abnormalities in metal content after the administration of toxic quantities of carbon tetrachloride to rats.