Chiang C S, Mason K A, Withers H R, McBride W H
Department of Radiation Oncology, UCLA Medical Center 90024-1714.
Int J Radiat Oncol Biol Phys. 1992;24(5):929-37. doi: 10.1016/0360-3016(92)90477-y.
The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.
本研究的目的是通过监测髓鞘碱性蛋白和2',3'-环核苷酸磷酸二酯酶水平的生化变化，探讨豚鼠放射性脊髓病的病理和细胞基础。用不同剂量的中子或钴γ射线照射豚鼠的腰部区域。中子和钴照射导致麻痹的半数有效剂量（ED50）分别为17.2 Gy和67.5 Gy，并且在组织学上与脱髓鞘有关。在麻痹开始时取自动物的脊髓中，髓鞘碱性蛋白水平与辐射剂量呈直接关系降低。导致麻痹的最低剂量使髓鞘碱性蛋白水平降低了25%。在另一项实验中，在导致麻痹的时间段内测量脊髓中髓鞘碱性蛋白的变化。令人惊讶的是，在4周照射期结束后立即发现髓鞘碱性蛋白减少。这些髓鞘碱性蛋白的早期变化并非明显的剂量依赖性，且在未导致麻痹的剂量下也会发生。仅在麻痹即将开始前才发现剂量依赖性降低。在相同标本中测量的2',3'-环核苷酸磷酸二酯酶（CNPase）活性变化与髓鞘碱性蛋白的变化基本相似。在脑脊液中，髓鞘碱性蛋白水平在麻痹开始前基本保持恒定。本研究表明，通过髓鞘相关蛋白髓鞘碱性蛋白和2',3'-环核苷酸磷酸二酯酶水平评估的脱髓鞘可在脊髓照射后不久发生，但只有在麻痹即将开始前才会出现明显的剂量依赖性变化。尽管脑脊液中髓鞘碱性蛋白的增加与放射性脊髓病的发生有关，但其检测不太可能预测这种辐射并发症。
