Department of Radiation Oncology, Wake Forest School of Medicine , Winston-Salem, North Carolina , USA.
Int J Radiat Biol. 2014 Sep;90(9):790-8. doi: 10.3109/09553002.2014.933915.
To determine if the brain's response to single doses predicts its response to 'biologically equivalent' fractionated doses.
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).
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).
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.
确定单次剂量的大脑反应是否能预测其对“生物学等效”分割剂量的反应。
用(137)Cs γ射线对年轻成年雄性 Fischer 344 大鼠进行全脑照射,单次剂量分别为 11、14 或 16.5 Gy,或采用“生物学等效”的 20、30 或 40 Gy 分割剂量(fWBI),每周两次,每次 5 Gy,分别照射 2、3 或 4 周。在照射后 2 个月,测量齿状回(DG)40 μm 切片中的炎症细胞标志物(总、激活和新生小胶质细胞)和神经发生(新生神经元)。
尽管未照射、单次剂量和 fWBI 大鼠 DG/海马体中的小胶质细胞总数没有显著差异(p > 0.7),但单次剂量显著增加了激活的小胶质细胞百分比(p < 0.003);fWBI 则没有(p > 0.1)。此外,单次剂量导致存活的新生小胶质细胞数量呈显著的剂量依赖性增加(p < 0.002);fWBI 则没有(p < 0.8)。尽管单次和 fWBI 剂量对 DG 中的总增殖都有同等的抑制作用,但单次剂量导致存活的新生神经元数量呈显著的剂量依赖性减少(p < 0.02);fWBI 则没有(p > 0.6)。
这些数据表明,大鼠大脑对单次剂量的细胞反应通常不能预测其对“生物学等效”分割剂量的细胞反应。