MICROSOMAL SPHINGOMYELIN ACCUMULATION IN THIOACETAMIDE-INJURED REGENERATING RAT-LIVER - INVOLVEMENT OF SPHINGOMYELIN SYNTHASE ACTIVITY

The purpose of this work was to determine whether alterations in the l ipid composition of rat liver microsomal membranes existed during thio acetamide-induced injury prior to the development of hepatic cancer an d biochemical mechanisms involved. Rats were injected intraperitoneall y with (50 mg/kg body wt per day) thioacetamide or diluent for 8 days. Liver homogenates and microsomal membranes from liver homogenates wer e obtained. Incorporation of [P-32]orthophosphate into whole liver lip ids and hepatic microsomal lipids was evaluated 75 min after isotope a dministration. These determinations were made after two separate perio ds of treatment (3 and 8 days). Activity of sphingomyelin synthase was assayed in rat liver homogenates as well as in the purified microsoma l fractions. Results demonstrated a maintenance of liver and hepatic m icrosomal contents of phosphatidylcholine during thioacetamide-induced injury even when the biosynthesis of this glycerophospholipid in both liver and their microsomal fractions appeared decreased. Also observe d was a considerable increase of microsomal sphingomyelin, as well as an increased hepatic biosynthesis of sphingomyelin caused by thioaceta mide treatment. The microsomal sphingomyelin/phosphatidylcholine radio activity ratio significantly increased. Sphingomyelin synthase activit y in liver homogenate appeared stimulated. In conclusion, our data are consistent with a thioacetamide-induced increase in microsomal sphing omyelin by a stimulation of sphingomyelin synthase. Based on this and previous studies, accumulation of sphingomyelin in the microsomal puri fied fraction is associated with the number of thioacetamide doses and is an early event clearly detected prior to tumoral characteristics o f hepatocytes.