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

蛋白激酶 C 激活剂对辐射诱导转化的调节作用

基本信息

批准号：
63580166
负责人：
KOMATSU Kenshi
金额：
$ 1.47万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63580166/
关键词：
Protein kinase C Transformation Radiation-incued cancer C3H10T1 2 cell Phorbol estel H-7 プロティンキナーゼC トランスフォーメーション

项目摘要

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.

用蛋白激酶C（PKC）激活剂α-凝血酶（TB）和1.2-二辛酰甘油（DOG）及PKC抑制剂1-（5-异喹啉磺酰基）-2，甲基哌啶二氢苯并吡喃（H-7）。α-凝血酶可增强细胞生长和平板接种效率：在10 μ g/ml TB存在下，23.5小时的细胞倍增时间减少到11.6小时，并且在100 μ g/ml TB存在下，平板接种效率增加到6倍以上。然而，辐射诱导的损伤可能不会被TB改变，因为4Gy照射的细胞的平板效率对TB浓度的依赖性与未照射的细胞相同。结核病转化率的研究显示了意想不到的结果; e.在50 μ g/ml TB存在下，4Gy照射的细胞的转化降低到60%。PKC的另一种激活剂DOG在10 μ g/ml DOG存在下也降低了用4戈伊照射的细胞的转化发生率：约为单独用X射线照射的细胞的发生率的一半。另一方面，PKC抑制剂H-7降低了经4戈伊照射的细胞的转化率，10 μ g/ml的H-7使其转化率降低至未处理细胞的十分之一。TPA处理的细胞也有这种抑制作用，其发生率比X射线单独处理的细胞高20 - 30%，而X射线和TPA联合处理的细胞则降低了近一半。最近Hei等报道，转染PKC基因的C3 H 10 T1/2细胞在4戈伊照射下仍无转化，这与本文报道的PKC激活剂降低转化率的结果一致。