Correlation between the Dynamic Changes of Lipids and Phospholipases during Induced Hepatocarcinogenesis

The correlation between the dynamic changes of l,2-diacylglyceride (DAG), phospholipids and phospholipase during the diethylnitrosoamine-induced hepatocarcinogenesis in rat was studied. It was found that liver DAG increased to the first peak at week 8 and maintained on a higher than normal level until week 14 when the second highest peak appeared, then gradually dropped. The composition of phospholipid was estimated simultaneously in order to elucidate the origin of DAG. It was discovered that only phosphatidylcholine (PC) and phosphatidylinositides decreased during liver carcinogenesis, suggesting these two phospholipids may be the origin of the increased DAG. PC was probably the major source of DAG, owing to the decreased amount of PIs which was not sufficient to generate the increased amount of DAG. Then the activities of PC-specific phospholipase C (PC-PLC) and phospholipase D (PLD) were determined by means of enzyme-coupling colorimetric methods. The results showed that the marked elevation of these two enzymes at week 8 might be related to the first peak of. DAG concentration and the PC hydrolysed by PC-PLC might be responsible for the second peak of DAG at week 14. The decline of DAG after week 14 was possibly due to the gradually decrease of PLD activity beginning from week 10, but other unknown factors might also be responsible for this decline. The regulation of PC-PLC and PLO by protein kinase C and related oncogenes were discussed.