Enhanced activity of deoxycytidine kinase after pulsed low dose rate and single dose gamma irradiation.
In both pulsed low dose rate (LDR) and single high dose radiation schedules, gemcitabine pretreatment sensitizes tumor cells to radiation. These radiosensitizing effects could be the result of decreased DNA repair. In this study, the effect of irradiation on the deoxycytidine kinase (dCK) needed for DNA repair was investigated. The activity of dCK, a deoxynucleoside analogue-activating enzyme was increased upon irradiation in both schedules. No change in dCK protein expression was observed that indicates a post-translational regulation. The benefit of this increased activity induced by irradiation should be further investigated in combination with deoxynucleoside analogues activated by this enzyme.
Sigmond
J
J
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Haveman
J
J
Kreder
N Castro
NC
Loves
W J
WJ
van Bree
C
C
Franken
N A
NA
Peters
G J
GJ
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D004260:DNA Repair; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003842:Deoxycytidine Kinase / Q000096:biosynthesis*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013997:Time Factors; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D004247:DNA; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine