title: Microvascular function regulates intestinal crypt response to radiation.
abstract: Recent evidence suggests that microvascular endothelial apoptosis represents the primary lesion in radiation damage to the gastrointestinal (GI) tract. Rescue of endothelium by depletion of acid sphingomyelinase or i.v. treatment with basic fibroblast growth factor (FGF) prevented the lethal GI syndrome in C(57)Bl/6 mice. Here we show that basic FGF increased crypt survival after irradiation by 2-3 fold, with a dose modification factor at D(10) of 1.15 (P < 0.01). Basic FGF inhibited initial crypt damage, assessed by crypt shrinkage at 18-24 h, but did not significantly affect the regeneration of surviving crypts at 3.5 days after irradiation. These data suggest that microvascular function regulates expression of radiation-induced crypt stem cell clonogen damage in the evolution of radiation injury to the GI mucosa.
authors.affiliation: Laboratory of Signal Transduction, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
authors.forename: Jerzy G
authors.initials: JG
authors.lastname: Maj
authors.forename: François
authors.initials: F
authors.lastname: Paris
authors.forename: Adriana
authors.initials: A
authors.lastname: Haimovitz-Friedman
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Richard
authors.initials: R
authors.lastname: Kolesnick
authors.forename: Zvi
authors.initials: Z
authors.lastname: Fuks
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000098:blood supply / Q000528:radiation effects; D007583:Jejunum / Q000098:blood supply* / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016222:Fibroblast Growth Factor 2