Radiation-induced changes in nucleotide metabolism of two colon cancer cell lines with different radiosensitivities.
OBJECTIVE
To investigate changes in nucleotide metabolism after irradiation.


METHODS
HT29 and SW48 human colon carcinoma cells were exposed to 60Co gamma-rays at doses ranging from 0 to 7.5 Gy. At different times after irradiation, the activities of nine enzymes involved in nucleotide metabolism were measured, the levels of thymidine kinase and deoxycytidine kinase proteins were evaluated by Western blot, and cell-cycle kinetics were analysed by flow cytometry.


RESULTS
Changes in enzyme activities concerned not purine but pyrimidine metabolism and essentially the salvage pathway for deoxyribonucleotide synthesis. They were greater in the less radiosensitive HT29 cells. The levels of thymidine kinase and deoxycytidine kinase proteins changed in parallel with their activities. The metabolic changes in irradiated cells did not seem to be due to S-phase transition and the pattern of enzyme activity changes was different from that observed in proliferative cells.


CONCLUSIONS
Radiation-induced changes in the salvage pathway for pyrimidine deoxyribonucleotide synthesis were observed. These findings could be exploited in cancer therapy because higher enzyme activities after irradiation suggest that radiation exposure may render cells more sensitive to the drugs activated by these enzymes.
Wei
S
S
CEA, DSV/DRR/LRE, Fontenay-aux-Roses, France. luccioni@dsvidf.cea.fr
Ageron-Blanc
A
A
Petridis
F
F
Beaumatin
J
J
Bonnet
S
S
Luccioni
C
C
D002453:Cell Cycle / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D003842:Deoxycytidine Kinase / Q000528:radiation effects; D005434:Flow Cytometry; D005720:Gamma Rays; D019073:HT29 Cells; D006801:Humans; D009711:Nucleotides / Q000378:metabolism*; D011829:Radiation Dosage; D011836:Radiation Tolerance; D013937:Thymidine Kinase / Q000528:radiation effects; D013940:Thymidylate Synthase / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014541:Uridine Kinase / Q000528:radiation effects
D003037:Cobalt Radioisotopes; D009711:Nucleotides; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D014541:Uridine Kinase; D003842:Deoxycytidine Kinase