Woudstra E C, Konings A W, Jeggo P A, Kampinga H H
Department of Radiobiology, University of Groningen, Groningen, The Netherlands.
Radiat Res. 1999 Aug;152(2):214-8.
Thermal radiosensitization is thought to result from inhibition of repair of radiation-induced DNA damage, DNA double-strand breaks in particular. Since the DNA-dependent protein kinase (DNA-PK) complex plays a major role in the nonhomologous end-joining of DSBs, it has been suggested that inactivation of this complex as a whole or of its individual subunits by heat might be involved in radiosensitization by heat. To test this hypothesis further, the ability of heat to enhance the radiosensitivity of cells proficient or deficient in either Ku80 or the DNA-PK catalytic subunit (DNA-PKcs) was investigated. In cells of two Ku80-deficient and two DNA-PKcs-deficient and double-strand break-deficient cell lines, the extent of radiosensitization by heat was not reduced compared to that in both their isogenic gene-complemented counterparts as well as to that in their parental cells. Thus radiosensitization by hyperthermia can be obtained irrespective of the Ku80 or DNA-PKcs status in cells. Therefore, Ku80 or DNA-PKcs and hence nonhomologous DSB end-joining do not play a crucial role in the enhancement of cellular radiosensitivity by hyperthermia.
热放射增敏作用被认为是由于辐射诱导的DNA损伤修复受到抑制，尤其是DNA双链断裂。由于DNA依赖性蛋白激酶（DNA-PK）复合物在双链断裂的非同源末端连接中起主要作用，有人提出，热使该复合物整体或其单个亚基失活可能与热放射增敏有关。为了进一步验证这一假设，研究了热增强Ku80或DNA-PK催化亚基（DNA-PKcs）功能正常或缺陷的细胞放射敏感性的能力。在两个Ku80缺陷、两个DNA-PKcs缺陷以及双链断裂缺陷的细胞系中，与它们各自的同基因基因互补对应物以及亲代细胞相比，热放射增敏的程度并未降低。因此，无论细胞中的Ku80或DNA-PKcs状态如何，均可实现热疗放射增敏。所以，Ku80或DNA-PKcs以及非同源双链断裂末端连接在热增强细胞放射敏感性方面并不起关键作用。
