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 Editorial Committee
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
37 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.