Kojima Shuji
Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda City, Japan.
Yakugaku Zasshi. 2006 Oct;126(10):849-57. doi: 10.1248/yakushi.126.849.
We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.
我们首先研究了低剂量γ射线照射后小鼠体内谷胱甘肽的诱导与免疫功能之间的关系。此后，在接种艾氏实体瘤（EST）的小鼠中证实了辐射对肿瘤生长的抑制作用。照射后不久，脾细胞的总谷胱甘肽水平短暂升高，并在照射后约4小时达到最大值。此后，到照射后24小时，该水平恢复到0小时时的值。照射后4小时也观察到显著高的脾细胞增殖反应。自然杀伤（NK）活性也以类似方式显著增加。反应达到最大值的时间与γ射线照射小鼠中脾细胞总谷胱甘肽水平的最大值时间恰好吻合。向从正常小鼠获得的脾细胞中外源添加还原型谷胱甘肽，以剂量依赖的方式增强了增殖反应和NK活性。然后在接种EST的小鼠中研究了辐射对肿瘤生长的抑制作用。重复低剂量照射（0.5 Gy，接种前及接种后早期内照射4次）显著延迟了肿瘤生长。最后，研究了单次低剂量（0.5 Gy）全身γ射线照射对免疫平衡的影响，以阐明抗肿瘤免疫的潜在机制。辐射后，血液淋巴细胞中B细胞的百分比选择性降低，同时辅助性T细胞群体的百分比增加。从接种EST的小鼠制备的脾细胞培养物中，辐射后48小时，IFN-γ水平显著升高，而IL-4水平未改变。辐射也增强了巨噬细胞分泌IL-12。这些结果表明，低剂量γ射线诱导Th1极化并增强杀肿瘤效应细胞的活性，从而导致肿瘤生长受到抑制。
