Role of DNA-PK subunits in radiosensitization by hyperthermia

Thermal radiosensitization is thought to result from inhibition of repair o f radiation-induced DNA damage, DNA double-strand breaks in particular. Sin ce the DNA-dependent protein kinase (DNA-PK) complex plays a major role in the nonhomologous end-joining of DSBs, it has been suggested that inactivat ion 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 in vestigated. In cells of two Ku80-deficient and two DNA-PKcs-deficient and d ouble-strand break-deficient cell lines, the extent of radiosensitization b y heat was not reduced compared to that in both their isogenic gene-complem ented counterparts as well as to that in their parental cells. Thus radiose nsitization 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 r adiosensitivity by hyperthermia. (C) 1999 by Radiation Research Society.