Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice

Gastrointestinal (GI) tract damage by chemotherapy or radiation Limits thei r efficacy in cancer treatment. Radiation has been postulated to target epi thelial stem cells within the crypts of Lieberkuhn to initiate the Lethal C II syndrome. Here, we show in mouse models that microvascular endothelial a poptosis is the primary Lesion Leading to stem cell dysfunction. Radiation- induced crypt damage, organ failure, and death from the CI syndrome were pr evented when endothelial apoptosis was inhibited pharmacologically by intra venous basic fibroblast growth factor (bFGF) or genetically by deletion of the acid sphingomyelinase gene. Endothelial but not crypt, cells express FG F receptor transcripts, suggesting that the endothelial Lesion occurs befor e crypt stem cell damage in the evolution of the GI syndrome. This study pr ovides a basis for new approaches to prevent radiation damage to the bowel.