Expression of thymidine kinase is essential to low dose radiation resistance of rat glioma cells.
We have found that thymidine kinase expression is a major radioresponse determinant in rat glioma cells. Cells that lack thymidine kinase expression are significantly more radiosensitive relative to the wild-type cells. The degree of sensitization is large, particularly at the dose levels used in fractionated radiotherapy. The difference in low dose survival can be accounted for by a marked difference in the ability of the cells to undergo repair of sublethal damage. When herpes thymidine kinase was introduced into the thymidine kinase-deficient mutant cells, radioresistance was partially restored, and sublethal damage repair was also enhanced. All other radiobiological responses, including DNA double-strand break repair, potentially lethal damage repair, G2 arrest, and cell cycle distribution, appeared similar among the cell lines. These data suggest that the thymidine kinase enzyme or its cellular gene may be an excellent therapeutic target to increase radiosensitivity and thereby, to enhance the radiocurability of malignant brain gliomas.
al-Nabulsi
I
I
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007.
Takamiya
Y
Y
Voloshin
Y
Y
Dritschilo
A
A
Martuza
R L
RL
Jorgensen
T J
TJ
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects*; D016195:G2 Phase; D005910:Glioma / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D051381:Rats; D013937:Thymidine Kinase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D013937:Thymidine Kinase