boron and Syndrome

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.

Topics: Animals; Apoptosis; Boron; Cesium Radioisotopes; Dose-Response Relationship, Radiation; Endothelial Cells; In Situ Nick-End Labeling; Intestine, Small; Isotopes; Jejunum; Liposomes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrons; Radiation Dosage; Radiation Injuries, Experimental; Syndrome; Whole-Body Irradiation

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.

Topics: Animals; Boron; Cell Survival; Dose-Response Relationship, Radiation; Endothelium, Vascular; Female; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Multipotent Stem Cells; Neutrons; Regeneration; Syndrome