title: The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.
abstract: OBJECTIVE
  Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replication. This investigation focuses on the combined effect of either fludarabine or gemcitabine and radiation on human squamous carcinoma cell lines in vitro, providing data for future decisions on head and neck chemoradiotherapy regimen.
  
  
  METHODS
  ZMK-1, A549, BW-225, GR-145, OH-65 and CaSki cell lines were incubated with either drug at defined schedules and irradiated at a single fraction dose of 2 Gy every 24 hours up to 8 Gy. Cytotoxic effects were measured by colony-forming assays, quantitative determination of apoptosis and isobologram analysis.
  
  
  RESULTS
  Incubation of fludarabine led to a radiosensitizing effect in the A549, CaSki and ZMK-1 cell lines and an additive effect in the BW-225, GR-145 and OH-65 cell lines. Treatment with gemcitabine only indicated significant radiosensitization in the CaSki cell line in combination with augmented resistance against gemcitabine application alone.
  
  
  CONCLUSIONS
  Our results reveal a potential radiosensitizing effect of fludarabine and its possible application in chemoradiotherapy of advanced head and neck carcinoma and possibly other tumor entities.
authors.affiliation: Department of Radiation Oncology, Georg-August-Universitat Gottingen, Gottingen.
authors.forename: Mirko
authors.initials: M
authors.lastname: Nitsche
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hermann
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Lucke
authors.forename: Kerstin
authors.initials: K
authors.lastname: Peters
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Frank
authors.forename: H
authors.initials: H
authors.lastname: Schmidberger
authors.forename: Olivier
authors.initials: O
authors.lastname: Pradier
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; D000093542:Gemcitabine