title: Not all 2 Gray radiation prescriptions are equivalent: Cytotoxic effect depends on delivery sequences of partial fractionated doses.
abstract: OBJECTIVE
  To test whether or not the commonly prescribed daily dose of 2 Gy (whole fraction), when delivered as various partial fraction (PF) dose sequences simulating clinical treatment fields, produces equal biologic effects.
  
  
  METHODS
  Eleven actively proliferating cell lines derived from human and animal tissues were used in this study. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and clonogenic assays were used to determine the radiation effects on cell proliferation and survival, respectively. The 2 Gy dose was divided into 2 or more PFs for delivery to simulate the delivery of clinical treatment fields. Most irradiation sequences contained two parts consisting of at least 1 small PF, denoted by S which was 0.5 Gy or less, and a large PF, denoted by L which was 1 Gy or more. Irradiation schemes were designed to include the following conditions: (a) the 2 Gy dose divided into combinations of an L-dose and one or more S-doses; (b) the L-dose given either before or after the S-doses; and (c) delivery of all partial fractions within a fixed total time.
  
  
  RESULTS
  Significant differences in biologic effect were observed between sequences in which the L-dose was given before or after the S-doses in both the MTT and clonogenic assays. Nearly all the latter schemes, that is S-L, produced greater cytotoxic effects than the L-S schemes.
  
  
  CONCLUSIONS
  These data demonstrate that the biologic effects of 2 Gy may differ in different clinical settings depending on the size and sequence of the partial fractions. The variation between cytotoxic effects is likely a result of the combination of low-dose hyper-radiosensitivity (HRS) and higher-dose increased radioresistance (IRR) effects established recently. We suggest that to ensure the optimal biologic effect of a prescribed dose of 2 Gy clinically, it is critical to consider the sequence in which the treatment fields are delivered when partial fractions of different sizes are used.
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, 401 College Street, Richmond, VA 23298, USA. plin@vcu.edu
authors.forename: Peck-Sun
authors.initials: PS
authors.lastname: Lin
authors.forename: Andrew
authors.initials: A
authors.lastname: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000502:physiology / Q000528:radiation effects*; D002470:Cell Survival; D004396:Coloring Agents; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D011836:Radiation Tolerance; D012062:Relative Biological Effectiveness; D013778:Tetrazolium Salts; D013844:Thiazoles; D014410:Tumor Stem Cell Assay
chemical_list: D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue