title: Caffeine-increased radiosensitivity is not dependent on a loss of G2/M arrest or apoptosis in bladder cancer cell lines.
abstract: OBJECTIVE
  Bladder cancer cell lines UCRU-BL-13, UCRU-BL-17/2 and UCRU-BL-28, with differing p53 status and molecular responses to irradiation, were used to investigate possible mechanisms for caffeine-induced radiosensitization.
  
  
  METHODS
  After treatment with caffeine and exposure to X-radiation, radiosensitivity was determined by clonogenic assay. Cell-cycle arrest and apoptosis were measured by flow cytometry.
  
  
  RESULTS
  Both BL-13 and BL-28 cells (each expressing p53 with a wild-type sequence) fail to arrest at the G2 checkpoint after radiation, but nevertheless caffeine did induce radiosensitization. In contrast, in BL-17/2 cells (expressing p53 with a point mutation in codon 280), caffeine treatment abrogated the radiation-induced G2 arrest but was not accompanied by radiosensitization. No effects on radiosensitivity were seen in RT112 cells (expressing a functionally defective p53) at low caffeine doses (2 mM), but at higher doses (4 mM and 10 mM) caffeine caused both abrogation of radiation-induced G2 arrest and radiosensitization. In none of the cell lines examined did caffeine treatment and/or irradiation result in apoptosis.
  
  
  CONCLUSIONS
  In contrast with previous studies, the data suggest that radiosensitization induced by caffeine is not dependent on abrogation of G2 arrest or the induction of apoptosis, and is not selective for cells expressing p53 proteins with mutations.
authors.affiliation: Oncology Research Centre, The Prince of Wales Hospital and Department of Medicine, The University of New South Wales, Randwick, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Ribeiro
authors.forename: A R
authors.initials: AR
authors.lastname: Barnetson
authors.forename: P
authors.initials: P
authors.lastname: Jackson
authors.forename: K
authors.initials: K
authors.lastname: Ow
authors.forename: M
authors.initials: M
authors.lastname: Links
authors.forename: P J
authors.initials: PJ
authors.lastname: Russell
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D002110:Caffeine