Schuller Bradley W, Rogers Arlin B, Cormier Kathleen S, Riley Kent J, Binns Peter J, Julius Richard, Hawthorne M Frederick, Coderre Jeffrey A
Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):205-10. doi: 10.1016/j.ijrobp.2006.12.069.
This report addresses the incidence of vascular endothelial cell apoptosis in the mouse small intestine in relation to the radiation-induced gastrointestinal (GI) syndrome.
Nonanesthetized mice received whole-body irradiation at doses above and below the threshold for death from the GI syndrome with 250 kVp X-rays, (137)Cs gamma rays, epithermal neutrons alone, or a unique approach for selective vascular irradiation using epithermal neutrons in combination with boronated liposomes that are restricted to the blood. Both terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining for apoptosis and dual-fluorescence staining for apoptosis and endothelial cells were carried out in jejunal cross-sections at 4 h postirradiation.
Most apoptotic cells were in the crypt epithelium. The number of TUNEL-positive nuclei per villus was low (1.62 +/- 0.03, mean +/- SEM) for all irradiation modalities and showed no dose-response as a function of blood vessel dose, even as the dose crossed the threshold for death from the GI syndrome. Dual-fluorescence staining for apoptosis and endothelial cells verified the TUNEL results and identified the apoptotic nuclei in the villi as CD45-positive leukocytes.
These data do not support the hypothesis that vascular endothelial cell apoptosis is the cause of the GI syndrome.
本报告探讨小鼠小肠血管内皮细胞凋亡发生率与辐射诱导的胃肠(GI)综合征之间的关系。
未麻醉小鼠接受全身照射,照射剂量高于或低于因胃肠综合征致死的阈值,照射方式包括250 kVp X射线、(137)Csγ射线、单独的超热中子,或采用超热中子与限于血液的硼化脂质体相结合的独特选择性血管照射方法。照射后4小时,在空肠横切面上进行凋亡的末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记(TUNEL)染色以及凋亡与内皮细胞的双荧光染色。
大多数凋亡细胞位于隐窝上皮。对于所有照射方式,每个绒毛的TUNEL阳性核数量较低(1.62±0.03,平均值±标准误),并且即使剂量超过因胃肠综合征致死的阈值,也未显示出作为血管剂量函数的剂量反应。凋亡与内皮细胞的双荧光染色证实了TUNEL结果,并将绒毛中的凋亡核鉴定为CD45阳性白细胞。
这些数据不支持血管内皮细胞凋亡是胃肠综合征病因的假说。