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Microvascular function regulates intestinal crypt response to radiation.

Jerzy G Maj1, François Paris, Adriana Haimovitz-Friedman

  • 1Laboratory of Signal Transduction, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Cancer Research
|August 9, 2003
PubMed
Summary
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Basic fibroblast growth factor (FGF) protects the gastrointestinal tract from radiation damage by preserving microvascular endothelial cells. This finding suggests microvascular function is key to mitigating radiation-induced intestinal injury.

Area of Science:

  • Radiation oncology
  • Gastrointestinal research
  • Vascular biology

Background:

  • Radiation damage to the gastrointestinal (GI) tract primarily involves microvascular endothelial apoptosis.
  • Previous studies indicated that depleting acid sphingomyelinase or administering basic fibroblast growth factor (FGF) could prevent lethal GI syndrome in mice.

Purpose of the Study:

  • To investigate the protective effects of basic FGF on radiation-induced GI damage.
  • To determine the impact of basic FGF on crypt survival and regeneration post-irradiation.

Main Methods:

  • Treatment of C(57)Bl/6 mice with basic FGF before irradiation.
  • Assessment of crypt survival and damage (shrinkage) at specific time points (18-24 hours and 3.5 days) post-irradiation.
  • Calculation of the dose modification factor (DMF) for basic FGF.

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Main Results:

  • Basic FGF increased intestinal crypt survival by 2-3 fold after irradiation.
  • A dose modification factor (DMF) at D(10) of 1.15 was observed for basic FGF (P < 0.01).
  • Basic FGF inhibited early crypt shrinkage but did not significantly alter the regeneration of surviving crypts.

Conclusions:

  • Microvascular endothelial cell protection by basic FGF is crucial for preventing acute radiation-induced GI syndrome.
  • Microvascular function plays a significant role in regulating radiation-induced damage to intestinal crypt stem cell clonogens.
  • Basic FGF demonstrates potential as a radioprotective agent for the GI tract.