The physiological state as a modifier of radiation-induced cytotoxicity in heterogeneous murine tumor cells growing in vitro.
The oxic radiation response (cytotoxicity) of two heterogeneous murine tumor-cell lines cultured in vitro was studied as a function of the cell's physiological state at the time of X-irradiation. The proliferating (P) 66 and 67 cells displayed equal radiosensitivities; however, the quiescent (Q) cells were considerably more radiosensitive than the P cells, and the 66Q cells were even more radiosensitive than the 67Q cells. Also, the 66Q cells continued to proliferate slowly with about 85 per cent in the G1 phase and 10 per cent in the S phase, while the 67 Q cells displayed a more complete G1 arrest (92-95 per cent). A detailed analysis of the metabolic status vs cell-cycle age (i.e. G1 vs S phase) indicated that the cell-cycle age was the predominant factor influencing radiation-induced cytotoxicity in 67 cells. The data also showed that in the plateau phase Q-cell cultures, pH and cell contact were not influencing factors and that the increased radiosensitivity of the Q cells could not be explained on the basis of energy deprivation. Moreover, the 66Q, but not the 67Q cells displayed an increased sensitivity in addition to that caused by the predominant cell-cycle age shift. This extra increase in radiosensitivity is of unknown metabolic origin, but could be related to cellular membrane fragility in the stressed 66Q cells since this extra component of Q-cell radiosensitivity was reduced both by refeeding (metabolic activation) 4 h before X-irradiation and by delayed plating while incubating the cells in Q medium at 37 degrees C after X-irradiation.
Cheng
W Y
WY
Shanghai Institute of Radiation Medicine, Shanghai Medical University, People's Republic of China.
Ridinger
D N
DN
Lehman
C M
CM
Puryear
R L
RL
Dethlefsen
L A
LA
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D002469:Cell Separation; D002470:Cell Survival / Q000528:radiation effects*; D004734:Energy Metabolism / Q000528:radiation effects; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D005947:Glucose