著者
Tetsuo YAMAMOTO Manabu KINOSHITA Nariyoshi SHINOMIYA Sadayuki HIROI Hidekazu SUGASAWA Yoshitaro MATSUSHITA Takashi MAJIMA Daizoh SAITOH Shuhji SEKI
出版者
Journal of Radiation Research 編集委員会
雑誌
Journal of Radiation Research (ISSN:04493060)
巻号頁・発行日
vol.51, no.2, pp.145-156, 2010 (Released:2010-03-25)
参考文献数
38
被引用文献数
20 28

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.