CHANGES OF PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE-C IN HEPATOCARCINOGENESIS AND IN THE PROLIFERATION AND DIFFERENTIATION OF RAT-LIVER CANCER-CELLS

The biological significance of phosphatidylcholine-specific phospholip ase C (PC-PLC) in hepatocarcinogenesis and the proliferation and diffe rentiation of rat liver cancer cells was investigated. The Ca2+-depend ent activities of PC-PLC gradually increased during N-nitrosodiethylam ine (DEN)-induced hepatocarcinogenesis and peaked at weeks 18-20 when the tumour formed. There was a close relationship between Ca2+-depende nt PC-PLC activities and cellular DNA content, membranous gamma-glutam yltranspeptidase (gamma-GT), and tyrosine protein kinase. In contrast, Ca2+-independent PC-PLC activities decreased during hepatocarcinogene sis. Similarly, when CBRH-7919 rat liver cancer cells were treated wit h phorbol 12-myristate 13-acetate, a proliferation stimulator of the c ells, gamma-GT and Ca2+-dependent activities of PC-PLC and the express ion of alpha-fetoprotein increased significantly. However, when these cells were induced by retinoic acid to differentiate, Ca2+-dependent P C-PLC and gamma-GT activities decreased significantly, together with a -fetoprotein expression. There was a close relationship between Ca2+-d ependent PC-PLC and gamma-GT activities during differentiation as ther e was during proliferation. We suppose that Ca2+-dependent PC-PLC is i nvolved in rat hepatocarcinogenesis induced by DEN and that it plays a n important role in the phorbol ester-induced proliferation or retinoi c acid-induced differentiation of liver cancer cells. (C) Academic Pre ss Limited.