Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Proceedings of the National Academy of Sciences of the United States of America
Bradley W SchullerJeffrey A Coderre

Abstract

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 end...Continue Reading

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