Jones Jeffrey A, Riggs Penny K, Yang Tracy C, Pedemonte Carlos H, Clarke Mark S F, Feeback Daniel L, Au William W
NASA Johnson Space Center, Medical Operations, Houston, TX 77058, USA.
Aviat Space Environ Med. 2007 Apr;78(4 Suppl):A67-78.
The bioeffects of space radiation on organisms outside of the environment of Earth's magnetosphere are a concern for long-duration exploration spaceflights. Potential mutagenic effects from space radiation exposure result from direct DNA damage or indirectly from the production of reactive oxygen species (ROS).
Normal human and canine lung, breast, and renal epithelial cells were assayed in vitro and exposed to escalating doses of gamma or heavy-ion carbon (290 MeV/u), ceon (400 MeV/u), or iron (600 MeV/u) irradiation. Post-exposure measurements of TER, lipid peroxidation (LP) via measurement of 4-hydroxy-nonenal (4-HNE), and malonaldehyde (MDA) and assessment of chromosome damage via fluorescence in situ hybridization with tandem labeling of chromosome 1 were performed.
Cells exposed to intermediate or high doses of radiation (5, 10, and 25 Gy) showed characteristic diminution in TER, thought to be secondary to dysfunction of tight junctions, and associated with membrane LP and other mechanisms. The cells also showed increases in 4-HNE + MDA measurements and increased frequency of chromosomal aberrations. Preliminary studies of cells incubated with media containing a combination of chemoprotective agents at the time of radiation exposure showed a 15-50% reduction in the radiation-induced changes in membrane resistance, levels of LP, and chromosomal aberrations relative to their unprotected cellular counterparts.
TER measurement, in conjunction with measures of LP, may provide a useful model for determination of physiological changes caused by radiation exposure and the efficacy of chemoprotective agents. A multi-agent mixture of chemoprotective agents may be more effective than previously evaluated single agents alone.
对于长期的太空探索飞行而言，地球磁层环境之外的太空辐射对生物体的生物效应令人担忧。太空辐射暴露可能产生的诱变效应源于DNA的直接损伤，或间接源于活性氧（ROS）的产生。
1）细胞培养单层中的跨上皮电阻（TER）测量可作为一种模型系统，用于检测暴露于模拟太空辐射所产生的细胞损伤，并用于测试潜在的化学防护剂；2）定量间接辐射效应的暴露生物标志物可用于预测细胞DNA损伤；3）一种多剂化学预防鸡尾酒可能会降低模拟太空辐射的生物效应。
对正常人类和犬类的肺、乳腺和肾上皮细胞进行体外测定，并使其暴露于递增剂量的γ射线或重离子碳（290兆电子伏特/核子）、氖（400兆电子伏特/核子）或铁（600兆电子伏特/核子）辐射下。在暴露后测量TER、通过测量4-羟基壬烯醛（4-HNE）和丙二醛（MDA）来测定脂质过氧化（LP），并通过对1号染色体进行串联标记的荧光原位杂交来评估染色体损伤。
暴露于中等或高剂量辐射（5、10和25戈瑞）的细胞显示出TER的特征性降低，这被认为是紧密连接功能障碍的继发结果，并与膜LP及其他机制相关。这些细胞还显示出4-HNE + MDA测量值增加以及染色体畸变频率增加。对在辐射暴露时与含有化学防护剂组合的培养基一起孵育的细胞进行的初步研究表明，相对于未受保护的细胞对应物，辐射诱导的膜电阻变化、LP水平和染色体畸变降低了15%至50%。
TER测量与LP测量相结合，可能为确定辐射暴露引起的生理变化以及化学防护剂的功效提供一个有用的模型。多种化学防护剂的混合物可能比之前评估的单一化学防护剂更有效。
