title: Strategies for the analysis of in vitro radiation sensitivity and prediction of interaction with potential radiation modifying agents.
abstract: OBJECTIVE
  To better predict radiation-drug interactions in in vitro model systems, thorough assessment of the effects of in vitro exposure is required. The aim of this article is to show that both clonogenic capacity and cellular proliferation, which represent important different elements of tumour conduct, can be considered when assessing in vitro radio sensitisation.
  
  
  METHODS
  A model was designed that can predict radiation-drug interactions based on changes in clonogenic capacity and cell proliferation by radiation modifying agents.
  
  
  RESULTS
  Using this mechanistical model, the effect of combined exposure to radiation and potential drugs can be tested on both established cell lines and primary cells. In addition, we could obtain more information about the mechanisms underlying the radiation-drug interaction by assessing the results of in vitro exposure on tumour cell proliferation and clonogenic capacity according to our model.
  
  
  CONCLUSIONS
  The significance of our model is not to replace the clonogenic gold standard but to give additional information about the radiation-drug combination by determining cell proliferation. Moreover, the advantage is that the interaction can also be predicted in cases where a clonogenic assay is not possible. Additional research into the biological effect of potential radio-sensitisers is warranted for future (pre)clinical studies.
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Luttjeboer
authors.forename: M Vincent M
authors.initials: MV
authors.lastname: Lafleur
authors.forename: Zinia J
authors.initials: ZJ
authors.lastname: Kwidama
authors.forename: Johannes
authors.initials: J
authors.lastname: Van Rijn
authors.forename: Jaap
authors.initials: J
authors.lastname: Van Den Berg
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Slotman
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cloos
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D054697:Cytostatic Agents / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D008954:Models, Biological; D011836:Radiation Tolerance / Q000187:drug effects*; D051381:Rats; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D054697:Cytostatic Agents