In vivo radioprotection of mouse brain endothelial cells by Hoechst 33342.

Abstract

Radiation-induced loss of mouse brain endothelial cells has been examined in mice given an intravenous injection of the DNA-binding radioprotector Hoechst 33342 (80 mg kg-1). At the time of irradiation, 10 min after injection, Hoechst fluorescence in the brain was confined to the endothelial cells. Endothelial cell density was measured using a histochemical fluorescence technique that had been used previously to monitor post-irradiation changes in endothelial cell density in rat brain, in which it was shown that a sensitive subpopulation comprising about 15% of the endothelial cells was lost within 24 h of radiation exposure. The present study shows a similar dose-response for the control mice, with depletion of the sensitive subpopulation to 85% being almost complete after a dose of 2.5 Gy gamma-rays. However, in mice irradiated 10 min after Hoechst 33342 administration, doses between 12 Gy and 20 Gy were required to ablate these cells. The kinetics of cell loss and the rather large dose modification factor suggests that Hoechst 33342 may be suppressing an apoptotic response in this subpopulation. Whatever the mechanism involved, Hoechst 33342 clearly provides substantial protection against early radiation-induced endothelial cell loss. Further studies are necessary to determine the extent to which this initial protection translates into an improved long-term survival of the "protected" cells and, especially, to see whether this endothelial cell protection can ameliorate the later consequences of central nervous system irradiation, namely necrosis and paralysis.