No significant endothelial apoptosis in the radiation-induced gastrointestinal syndrome.
OBJECTIVE
This report addresses the incidence of vascular endothelial cell apoptosis in the mouse small intestine in relation to the radiation-induced gastrointestinal (GI) syndrome.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These data do not support the hypothesis that vascular endothelial cell apoptosis is the cause of the GI syndrome.
Schuller
Bradley W
BW
Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rogers
Arlin B
AB
Cormier
Kathleen S
KS
Riley
Kent J
KJ
Binns
Peter J
PJ
Julius
Richard
R
Hawthorne
M Frederick
MF
Coderre
Jeffrey A
JA
D000818:Animals; D017209:Apoptosis; D001895:Boron; D002588:Cesium Radioisotopes; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000502:physiology / Q000528:radiation effects*; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D007554:Isotopes; D007583:Jejunum / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009502:Neutrons; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology*; D013577:Syndrome; D014916:Whole-Body Irradiation
D002588:Cesium Radioisotopes; D007554:Isotopes; D008081:Liposomes; D001895:Boron