title: Cellular response of the rat brain to single doses of (137)Cs γ rays does not predict its response to prolonged 'biologically equivalent' fractionated doses.
abstract: OBJECTIVE
  To determine if the brain's response to single doses predicts its response to 'biologically equivalent' fractionated doses.
  
  
  METHODS
  Young adult male Fischer 344 rats were whole-brain irradiated with either single 11, 14, or 16.5 Gy doses of (137)Cs γ rays or their 'biologically equivalent' 20, 30, or 40 Gy fractionated doses (fWBI) delivered in 5 Gy fractions, twice/week for 2, 3, or 4 weeks, respectively. At 2 months post-irradiation, cellular markers of inflammation (total, activated, and newborn microglia) and neurogenesis (newborn neurons) were measured in 40 μm sections of the dentate gyrus (DG).
  
  
  RESULTS
  Although the total number of microglia in the DG/hilus was not significantly different (p > 0.7) in unirradiated, single dose, and fWBI rats, single doses produced a significant (p < 0.003) increase in the percent-activated microglia; fWBI did not (p > 0.1). Additionally, single doses produced a significant (p < 0.002) dose-dependent increase in surviving newborn microglia; fWBI did not (p < 0.8). Although total proliferation in the DG was reduced equally by single and fWBI doses, single doses produced a significant dose-dependent (p < 0.02) decrease in surviving newborn neurons; fWBI did not (p > 0.6).
  
  
  CONCLUSIONS
  These data demonstrate that the rat brain's cellular response to single doses often does not predict its cellular response to 'biologically equivalent' fWBI doses.
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine , Winston-Salem, North Carolina , USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Greene-Schloesser
authors.forename: Mitra
authors.initials: M
authors.lastname: Kooshki
authors.forename: Valerie
authors.initials: V
authors.lastname: Payne
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Wheeler
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Metheny-Barlow
authors.forename: Mike E
authors.initials: ME
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D049109:Cell Proliferation / Q000528:radiation effects; D002588:Cesium Radioisotopes / Q000737:chemistry*; D018891:Dentate Gyrus / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006624:Hippocampus / Q000528:radiation effects; D007249:Inflammation / Q000532:radiotherapy; D008297:Male; D017628:Microglia / Q000473:pathology; D055495:Neurogenesis / Q000528:radiation effects; D009474:Neurons / Q000528:radiation effects; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002588:Cesium Radioisotopes
keywords: Brain irradiation; fractionated dose responses; inflammation; neurogenesis; single dose responses