Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

J Radiat Res. 2010;51(2):145-56. doi: 10.1269/jrr.09078. Epub 2009 Dec 4.


While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / genetics
  • Ascorbic Acid / analysis
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Bone Marrow / pathology
  • Bone Marrow / radiation effects
  • Bone Marrow Transplantation
  • Caspases / metabolism
  • DNA Damage / drug effects
  • Diarrhea / etiology
  • Diarrhea / prevention & control*
  • Drug Evaluation, Preclinical
  • Free Radicals / blood
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / prevention & control*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / radiation effects
  • Intestinal Mucosa / ultrastructure
  • Intestine, Small / pathology
  • Intestine, Small / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Premedication*
  • Radiation Chimera
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / prevention & control*
  • Radiation-Protective Agents / analysis
  • Radiation-Protective Agents / pharmacology
  • Radiation-Protective Agents / therapeutic use*
  • Whole-Body Irradiation / adverse effects


  • Apoptosis Regulatory Proteins
  • Free Radicals
  • Radiation-Protective Agents
  • Caspases
  • Ascorbic Acid