title: Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: a cell line study in four glioblastoma multiforme (GBM) cell lines.
abstract: OBJECTIVE
  To determine if ultra-fractionation using repeated pulses of radiation (10 × 0.2 Gray [Gy]) would be more cytotoxic than continuously-delivered radiation to the same total dose (2 Gy) in four glioma cell lines.
  
  
  METHODS
  Human T98G, U373, U87MG and U138MG cells were conventionally X-irradiated with 0.1-8 Gy and clonogenic survival assessed. Next, cells were treated with either a single dose of 2 Gy or 10 pulses of 0.2 Gy using a 3-min inter-pulse interval and DNA (Deoxyribonucleic acid) repair (pHistone H2A.X), G2-phase cell cycle checkpoint arrest (pHistone H3) and apoptosis (caspase-3) compared between the two regimens. A dose of 0.2 Gy was selected as this reflects the hyper- radiosensitivity (HRS)/increased radioresistance (IRR) transition point of the low-dose cell survival curve.
  
  
  RESULTS
  T98G, U87MG and U138MG exhibited distinct HRS responses and survival curves were well-described by the Induced Repair model. Despite the prolonged delivery time, ultra-fractionation (10 × 0.2 Gy) was equally effective as a single continuously-delivered 2 Gy dose. However, ultra-fractionation was more effective when given for five consecutive days to a total dose of 10 Gy. The increased effectiveness of ultra-fractionation could not be attributed directly to differences in DNA damage, repair processes or radiation-induced apoptosis.
  
  
  CONCLUSIONS
  Ultra-fractionation (10 × 0.2 Gy) is an effective modality for killing glioma cell lines compared with standard 2 Gy dosing when multiple days of treatment are given.
authors.affiliation: Department of Radiation Oncology, Beaumont Health System , Royal Oak, Michigan , USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Schoenherr
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Krueger
authors.forename: Lynn
authors.initials: L
authors.lastname: Martin
authors.forename: Laure
authors.initials: L
authors.lastname: Marignol
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D008962:Models, Theoretical; D011836:Radiation Tolerance; D013778:Tetrazolium Salts; D013844:Thiazoles; D014965:X-Rays
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue