Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / radiation effects
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Apoptosis Regulatory Proteins / biosynthesis
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Apoptosis Regulatory Proteins / genetics
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Ascorbic Acid / analysis
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Ascorbic Acid / pharmacology
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Ascorbic Acid / therapeutic use*
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Bone Marrow / pathology
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Bone Marrow / radiation effects
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Bone Marrow Transplantation
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Caspases / metabolism
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DNA Damage / drug effects
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Diarrhea / etiology
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Diarrhea / prevention & control*
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Drug Evaluation, Preclinical
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Free Radicals / blood
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Gastrointestinal Hemorrhage / etiology
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Gastrointestinal Hemorrhage / prevention & control*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / radiation effects
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / radiation effects
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Intestinal Mucosa / ultrastructure
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Intestine, Small / pathology
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Intestine, Small / radiation effects
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Male
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Mice
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Mice, Inbred C57BL
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Premedication*
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Radiation Chimera
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Radiation Injuries, Experimental / etiology
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Radiation Injuries, Experimental / prevention & control*
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Radiation-Protective Agents / analysis
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Radiation-Protective Agents / pharmacology
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Radiation-Protective Agents / therapeutic use*
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Whole-Body Irradiation / adverse effects
Substances
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Apoptosis Regulatory Proteins
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Free Radicals
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Radiation-Protective Agents
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Caspases
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Ascorbic Acid