[Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].
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.
Kojima
Shuji
S
Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda City, Japan. kjma@rs.noda.tus.ac.jp
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002286:Carcinoma, Ehrlich Tumor / Q000532:radiotherapy; D049109:Cell Proliferation / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism*; D007109:Immunity / Q000528:radiation effects*; D018655:Lymphocyte Count; D051379:Mice; D011829:Radiation Dosage; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000528:radiation effects*; D018418:Th2 Cells / Q000276:immunology / Q000528:radiation effects; D014916:Whole-Body Irradiation
D016207:Cytokines; D005978:Glutathione