Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro.
OBJECTIVE
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.


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.
Latz
D
D
Department of Radiotherapy, University of Heidelberg, Germany.
Schulze
T
T
Manegold
C
C
Schraube
P
P
Flentje
M
M
Weber
K J
KJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D008545:Melanoma / Q000473:pathology*; D011829:Radiation Dosage; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D016019:Survival Analysis; D014407:Tumor Cells, Cultured / Q000166:cytology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
C012353:hydroperoxyisophosphamide; D007069:Ifosfamide