Modulating Effect of Protein Kinase C Activator on Radiation-Induced Transformation

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The effect of protein kinase C ( PKC ), known as receptor signals of cancer promotor agent, by X ray were investigated using PKC activator, alpha-thrombin ( TB ) and 1.2-dioctanoyl gycerol ( DOG ), and PKC inhibitor, 1- (5-isoquinoline sulfonyl) -2, methyl piperadine dihydrochrolide ( H-7 ).The alpha-thrombin can enhance the cell growth and plating efficiency: the cell doubling time of 23.5 hours were reduced to 11.6 hours in the presence of 10 ug/ml of TB and plating efficiency were increased to more than 6 times in the presence of 100 ug/ml of TB. However, radiation-induced damage may not be modified by TB, since the dependence of plating efficiency of 4 Gy-irradiated cells on TB concentration were same as that of non-irradiated cells. The study on transformation incidence with TB show the unexpected result ; i. e. the transformation of 4 Gy-irradiated cells were reduced to 60 %in the presence of 50 ug/ml of TB. Another activator of PKC, DOG, also decreased the transformation incidence of cells irradiated with 4 Gy in the presence of 10 ug/ml of DOG : about half of the incidence of cells irradiated with Xray alone. On the other hand, the H-7, PKC inhibitor, decrease the transformation incidence of cells irradiated with 4 Gy ; 10 ug/ml of H-7 reduced their incidence to one tenth of untreated cells. This inhibitory effect also occurred in TPA treated cells.Their incidency, which is higher than 20 - 30 % than that of cells treated with X ray alone, reduced to near half of that of cells in combination with X ray and TPA. Recently, Hei et al reported that C3H10T1/2 transfected with PKC gene indicated no transformant even when it is irradiated with 4 Gy.This is in agreement with the result presented here, where transformation incidences were reduced in the presence of PKC activators.