Hei T K, Geard C R, Hall E J
Int J Radiat Oncol Biol Phys. 1984 Aug;10(8):1255-9. doi: 10.1016/0360-3016(84)90328-6.
A study was made of the effects of cellular non-protein sulfhydryl (NPSH) depletion on cytotoxicity, cell cycle kinetics, oncogenic transformation and sister chromatid exchange (SCE) in C3H 10T1/2 cells. Using DL-Buthionine S-R-Sulfoximine (BSO) at a concentration of 0.05 mM to deplete thiols, it was found spectrophotometrically that less than 5% of control NPSH level remained in the cells after 24-hour treatment under aerated conditions. Such NPSH depleted cells, when subject to a 3 Gy gamma-ray treatment, were found to have no radiosensitizing response either in terms of cell survival or oncogenic transformation. In addition, decreased levels of NPSH had no effect on spontaneous or radiation-induced SCE nor were cell cycle kinetics additionally altered. Therefore, the inability of NPSH depletion to alter gamma-ray induced cellular transformation was unrelated to any possible effect of BSO on the cell cycle. These results suggest that, while endogenous NPSH depletion has been considered to play an important role for most radiosensitizers in clinical or preclinical use, such depletion may result in little or no additional oncogenic or genotoxic effects on aerated normal tissues.
研究了细胞非蛋白质巯基（NPSH）耗竭对C3H 10T1/2细胞的细胞毒性、细胞周期动力学、致癌转化和姐妹染色单体交换（SCE）的影响。使用浓度为0.05 mM的DL-丁硫氨酸S-R-亚砜亚胺（BSO）来消耗硫醇，通过分光光度法发现，在通气条件下处理24小时后，细胞中剩余的NPSH水平不到对照水平的5%。发现这种NPSH耗竭的细胞在接受3 Gy的γ射线处理后，在细胞存活或致癌转化方面均无放射增敏反应。此外，NPSH水平的降低对自发或辐射诱导的SCE没有影响，细胞周期动力学也没有额外改变。因此，NPSH耗竭无法改变γ射线诱导的细胞转化与BSO对细胞周期的任何可能影响无关。这些结果表明，虽然内源性NPSH耗竭被认为在临床或临床前使用的大多数放射增敏剂中起重要作用，但这种耗竭可能对通气的正常组织几乎没有或没有额外的致癌或基因毒性作用。
