PHOSPHOINOSITIDE TURNOVER DURING HEPATOCARCINOGENESIS INDUCED BY N-NITROSODIETHYLAMINE

The metabolism of phosphatidylinositol (PI) has been examined in rat liver during administration of N-nitrosodiethylamine (NDEA). The activities of PI kinase and PIP kinase were observed to be decreased as early as 7 days from the onset of NDEA administration, and remained suppressed until 60 days. PI sythetase showed a transient increase in activity at 7 days and thereafter the activity declined. The level of diacylglycerol (DAG), a key second messenger, showed a steady rise during the period of NDEA administration. A parallel increase in DAG kinase activity was also apparent. The results suggest that alterations of enzymes central to second messenger system with resulting changes in phosphoinositide turnover are important events during hepatocarcinogenesis induced by NDEA.