Cellular response of the rat brain to single doses of¹³⁷Cs γ rays does not predict its response to prolonged ‘biologically equivalent’ fractionated doses

Dana M. Greene-Schloesser*ae, Mitra Kooshkiae, Valerie Payneae, Ralph B. D’Agostino Jrb, Kenneth T. Wheelerce, Linda J. Metheny-Barlowade & Mike E. Robbinsadea Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USAb Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USAc Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USAd Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USAe the Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, North Carolina, USACorrespondence: Dr. Dana M. Greene-Schloesser, PhD, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27103, USA. Tel: + 1 336 713 7629. E-mail: dgreenes@wakehealth.eduAbstractPurpose: 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 137Cs 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.