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

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.