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Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro
D Latz1, T Schulze, C Manegold
1Department of Radiotherapy, University of Heidelberg, Germany.
Background And Purpose:
Combined radiochemotherapy has gained increasing interest in clinical applications. The effects of combined exposure of ionizing radiation and 4-hydroperoxyifosfamide (4HOOIF) on cell survival were investigated in vitro.
Materials And Methods:
Clonogenic survival of log phase V79, Caski (squamous carcinoma), Widr (colon carcinoma) and MRI-221 cells (human melanoma) was determined after combined exposure to 4HOOIF and radiation. Measurement of cell survival for different cell cycle phases was performed after mitotic shake-off (V79) or appropriate intervals after serum stimulation of plateau phase cells (Widr). Control of cell cycle distribution was performed using flow cytometry.
Results:
In all cell lines tested, a combined exposure resulted in cell killing that was greater than for independent action. While this type of radiosensitization was of minor magnitude for log-phase cells or cells in G1 substantial radiosensitization was detected for S-phase cells with enhancement ratios (calculated from the respective mean inactivation doses) of up to 1.5.
Conclusions:
The results demonstrate the interaction of 4HOOIF and radiation-induced cell damage with marked cell cycle specificity. Since the largest combination effect was observed for the most radioresistant S-phase cells, damage interaction could be mediated by an interference of 4HOOIF with the repair/fixation pathway of radiation-induced potentially lethal damage.