Schuller Bradley W, Binns Peter J, Riley Kent J, Ma Ling, Hawthorne M Frederick, Coderre Jeffrey A
Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3787-92. doi: 10.1073/pnas.0600133103. Epub 2006 Feb 27.
The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 +/- 0.04 Gy x min(-1). An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 microm) particles released from neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70-90 nm in diameter. Different liposome formulations produced 45 +/- 7 or 118 +/- 12 microg/g 10B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 +/- 0.09 or 1.90 +/- 0.16 Gy x min(-1), respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 +/- 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.
本文探讨了血管内皮细胞损伤在肠道隐窝干细胞丢失及随后胃肠道（GI）综合征发展过程中可能发挥的作用。小鼠接受了剂量率为0.57±0.04 Gy·min⁻¹的全身超热中子照射。通过将硼（¹⁰B）掺入直径70 - 90 nm的脂质体中，使中子俘获反应产生的短程（5 - 9微米）粒子选择性地靶向内皮细胞，这些粒子被限制在血液中。不同的脂质体制剂在中子照射时血液中产生的硼含量分别为45±7或118±12 μg/g，这导致内皮细胞中的总吸收剂量率分别为1.08±0.09或1.90±0.16 Gy·min⁻¹。照射后3.5天，肠道隐窝微集落试验表明，相对于非特异性全身中子束剂量，微血管剂量增加2至3倍，并未导致除中子束单独照射所产生的隐窝干细胞丢失之外的额外损失。仅接受中子束照射后因GI综合征死亡的阈值剂量为9.0±0.6 Gy。在血液中含有硼化脂质体且接受的中子束剂量<9.0 Gy的组中，尽管计算得出内皮细胞的吸收剂量高达27.7 Gy，但没有因GI综合征死亡的情况。这些数据表明，内皮细胞损伤并非肠道隐窝干细胞丢失及GI综合征最终发展的病因。
