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

采用PKC激活剂α -凝血酶（TB）、1.2-二辛烷酰甘油（DOG）和PKC抑制剂1-（5-异喹啉磺酰）-2、甲基哌拉定二氢氯化物（H-7）研究了PKC受体信号在X射线下的作用。α -凝血酶能提高细胞的生长和镀效率，在10 ug/ml TB存在下，细胞倍增时间由23.5小时缩短到11.6小时，在100 ug/ml TB存在下，镀效率提高到6倍以上。然而，TB可能不会改变辐射引起的损伤，因为4个gy辐照细胞的镀效率与未辐照细胞的镀效率对TB浓度的依赖性相同。结核病转化率的研究显示出意想不到的结果；即，在50 ug/ml的TB存在下，4个gy照射细胞的转化率降低到60%。另一种PKC激活剂DOG在10 ug/ml DOG存在时也降低了4 Gy照射细胞的转化发生率：约为单独x射线照射细胞发生率的一半。另一方面，PKC抑制剂H-7降低了4 Gy辐照下细胞的转化率；10 ug/ml的H-7将其发生率降低到未处理细胞的十分之一。这种抑制作用也发生在TPA处理的细胞中。它们的发生率比X射线单独治疗的细胞高20 - 30%，降至X射线和TPA联合治疗的细胞的近一半。最近Hei等报道了转染PKC基因的C3H10T1/2即使在4 Gy照射下也未发生转化。这与这里提出的结果一致，在PKC激活剂的存在下，转化发生率降低。

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.