The by-products generated during sarin synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity
The by-products generated during sarin synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity
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DOI：
10.1016/s0300-483x(00)00174-8
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发表时间：
2000-05-05
期刊：
影响因子：
4.5
通讯作者：
Minami, M
中科院分区：
文献类型：
--
作者：
Li, Q;Hirata, Y;Minami, M
东京地铁列车上有超过 5000 名乘客因神经毒气、沙林及其副产品受伤。对受害者尿液样本中沙林及其副产物的携磷代谢物进行分析表明，他们不仅接触了沙林，还接触了沙林合成过程中产生的副产物，即甲基膦酸二异丙酯（DIMP）和甲基膦酸二乙酯（DEMP）。我们怀疑沙林副产物造成的遗传后遗症，因此，我们检查了姐妹染色单体交换（SCE）的频率，发现受害者中的SCE明显高于对照组，并且DIMP和DEMP在体外显着诱导人淋巴细胞SCE。在本研究中，为了探讨诱导淋巴细胞高频率 SCE 的 DIMP 和 DEMP 是否也影响淋巴细胞功能，我们检测了 DIMP 和 DEMP 对小鼠脾自然杀伤 (NK) 和脾细胞毒性 T 淋巴细胞 (CTL) 活性以及体外人淋巴细胞 NK 活性的影响。我们发现 DIMP 和 DEMP 以剂量依赖性方式显着抑制 NK 和 CTL 活性。 DIMP诱导的抑制作用强于DEMP诱导的抑制作用。 DIMP和DEMP对小鼠脾NK活性的影响强于对脾CTL活性的影响，并且人淋巴细胞对DIMP和DEMP比小鼠脾细胞更敏感。 (C) 2000 Elsevier Science Ireland Ltd. 保留所有权利。
More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.