Kojima S, Teshima K, Yamaoka K
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan.
Anticancer Res. 2000 May-Jun;20(3A):1589-94.
We examined the mechanisms of the elevation of glutathione level induced in macrophage-like RAW 264.7 cells by low doses of gamma-rays. The level increased soon after exposure of the cells to 50 cGy of gamma-rays, peaked between 3 hours and 6 hours and returned almost to the time 0 value by 24 hours post-irradiation. Doses between 25 and 100 cGy significantly increased the glutathione level at 4 hours post-irradiation. However, there was no significant elevation at doses of more than 100 cGy or less than 25 cGy. When the effect of dose rate was examined at a constant absorbed dose of 50 cGy, dose rates of more than 50 cGy/minute significantly increased the GSH level at 4 hours post-irradiation. It was also shown that the elevation of glutathione level in cells irradiated with low doses of gamma-rays followed the induction of mRNA coding for gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the de novo glutathione synthesis pathway. When the cells were exposed to the radiation in the presence of genistein, calphostin C or nifedipine, the elevations of glutathione and gamma-GCS mRNA expression were both mostly blocked. EGTA also strongly inhibited these elevations. These results suggest that the tyrosine kinase, calcium channel and protein kinase C activities play an essential role in the low-dose-radiation-induced elevation of cellular glutathione.
我们研究了低剂量γ射线诱导巨噬细胞样RAW 264.7细胞内谷胱甘肽水平升高的机制。细胞暴露于50 cGy的γ射线后，谷胱甘肽水平很快升高，在3小时至6小时之间达到峰值，并在照射后24小时几乎恢复到初始值。25至100 cGy的剂量在照射后4小时显著提高了谷胱甘肽水平。然而，剂量超过100 cGy或低于25 cGy时，谷胱甘肽水平没有显著升高。当在恒定吸收剂量50 cGy下研究剂量率的影响时，剂量率超过50 cGy/分钟在照射后4小时显著提高了谷胱甘肽水平。研究还表明，低剂量γ射线照射的细胞内谷胱甘肽水平的升高伴随着编码γ-谷氨酰半胱氨酸合成酶（γ-GCS）的mRNA的诱导，γ-GCS是谷胱甘肽从头合成途径的限速酶。当细胞在染料木黄酮、钙泊三醇C或硝苯地平存在的情况下接受辐射时，谷胱甘肽和γ-GCS mRNA表达的升高大多被阻断。乙二醇双四乙酸（EGTA）也强烈抑制这些升高。这些结果表明，酪氨酸激酶、钙通道和蛋白激酶C活性在低剂量辐射诱导的细胞内谷胱甘肽升高过程中起重要作用。
