Weiss J F, Srinivasan V, Kumar K S, Landauer M R
Radiation Biochemistry Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5145, USA.
Adv Space Res. 1992;12(2-3):223-31. doi: 10.1016/0273-1177(92)90112-b.
The need exists for compounds that will protect individuals from high-dose acute radiation exposure in space and the agents that might be less protective but less toxic and longer acting. Metals and metal derivatives provide a small degree of radioprotection (dose reduction factor < or = 1.2 for animal survival after whole-body irradiation). Emphasis is placed here on the radioprotective potential of selenium (Se). Both the inorganic salt, sodium selenite, and the organic Se compound, selenomethionine, enhance the survival of irradiated mice (60Co, 0.2 Gy/min) when injected IP either before (-24 hr and -1 hr) or shortly after (+15 min) radiation exposure. When administered at equitoxic doses (one-fourth LD10; selenomethionine = 4.0 mg/kg Se, sodium selenite = 0.8 mg/kg Se), both drugs enhanced the 30-day survival of mice irradiated at 9 Gy. Survival after 10-Gy exposure was significantly increased only after selenomethionine treatment. An advantage of selenomethionine is lower lethal and behavioral toxicity (locomotor activity depression) compared to sodium selenite, when they are administered at equivalent doses of Se. Sodium selenite administered in combination with WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, enhances the radioprotective effect and reduces the lethal toxicity, but not the behavioral toxicity, of WR-2721. Other studies on radioprotection and protection against chemical carcinogens by different forms of Se are reviewed. As additional animal data and results from human chemoprevention trials become available, consideration also can be given to prolonged administration of Se compounds for protection against long-term radiation effects in space.
需要有能够保护个体免受太空高剂量急性辐射照射的化合物，以及那些防护性可能稍弱但毒性较小且作用时间更长的药剂。金属及其衍生物能提供一定程度的辐射防护（全身照射后动物存活的剂量降低因子≤1.2）。这里重点关注硒（Se）的辐射防护潜力。无机盐亚硒酸钠和有机硒化合物硒代蛋氨酸，在辐射暴露前（-24小时和-1小时）或暴露后不久（+15分钟）腹腔注射时，均可提高受辐照小鼠（60Co，0.2 Gy/分钟）的存活率。当以等毒性剂量给药时（四分之一LD10；硒代蛋氨酸=4.0毫克/千克硒，亚硒酸钠=0.8毫克/千克硒），两种药物均可提高9 Gy辐照小鼠的30天存活率。仅在硒代蛋氨酸治疗后，10 Gy照射后的存活率才显著提高。与亚硒酸钠相比，硒代蛋氨酸的一个优势在于，当以等效剂量的硒给药时，其致死毒性和行为毒性（运动活性降低）较低。亚硒酸钠与WR-2721（S-2-(3-氨丙基氨基)乙基硫代磷酸）联合给药，可增强辐射防护效果，并降低WR-2721致命毒性，但不降低其行为毒性。本文综述了关于不同形式的硒在辐射防护及预防化学致癌物方面的其他研究。随着更多动物数据和人类化学预防试验结果的出现，也可考虑长期给予硒化合物，以预防太空长期辐射效应。
