PHOSPHOINOSITIDE TURNOVER DURING HEPATOCARCINOGENESIS INDUCED BY N-NITROSODIETHYLAMINE

The metabolism of phosphatidylinositol (PI) has been examined in rat l iver during administration of N-nitrosodiethylamine (NDEA). The activi ties of PI kinase and PIP kinase were observed to be decreased as earl y as 7 days from the onset of NDEA administration, and remained suppre ssed until 60 days. PI sythetase showed a transient increase in activi ty at 7 days and thereafter the activity declined. The level of diacyl glycerol (DAG), a key second messenger, showed a steady rise during th e period of NDEA administration. A parallel increase in DAG kinase act ivity was also apparent. The results suggest that alterations of enzym es central to second messenger system with resulting changes in phosph oinositide turnover are important events during hepatocarcinogenesis i nduced by NDEA.