title: Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro.
abstract: 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.
authors.affiliation: Department of Radiotherapy, University of Heidelberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Latz
authors.forename: T
authors.initials: T
authors.lastname: Schulze
authors.forename: C
authors.initials: C
authors.lastname: Manegold
authors.forename: P
authors.initials: P
authors.lastname: Schraube
authors.forename: M
authors.initials: M
authors.lastname: Flentje
authors.forename: K J
authors.initials: KJ
authors.lastname: Weber
mesh_terms: 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*
chemical_list: C012353:hydroperoxyisophosphamide; D007069:Ifosfamide