Kiyonori Yamaoka

Increased SOD activities and decreased lipid peroxide levels induced by low dose X irradiation in rat organs

After a single exposure to doses ranging from 0.05 to 0.50 Gy, the SOD activities in immune organs of the irradiated rats, at 4 h after whole-body X irradiation, showed significant increases by 50 to 90% (hereinafter p less than 0.05) in comparison with the control groups. The dose in the brain and liver showed tendencies to increase by 30 to 50% for doses ranging from 0.50 to 2.50 Gy. The levels of TBARS (lipid peroxides) in immune organs decreased significantly by 20 to 50% in contrast with the control groups for doses ranging from 0.10 to 1.00 Gy. Decreases by 20 to 30% were observed in brains and livers for doses near 0.50 Gy. When the dose was 0.25 Gy, the SOD activities in the spleen showed a persistent radiation-induced increase for at least 12 weeks, livers for 8 weeks, brains and thymuses for 4 weeks, and bone marrows for about 1 week. The TBARS levels in the brain and thymus showed persistent decreases due to irradiation for at least 12 weeks, and those in bone marrows for 8 h.

A comprehensive review of radon emanation measurements for mineral, rock, soil, mill tailing and fly ash.

To our knowledge, this paper is the most comprehensive review to cover most studies, published in the past three decades at least, of radon emanation measurements. The radon emanation fraction, a possibility of radon atoms generated in a material escaping from its grains, has been widely measured for a variety of materials. The aim of this review is to organize a huge number of such data accumulated. The representative values of the emanation fraction for minerals, rocks, soils, mill tailings and fly ashes were derived to be 0.03, 0.13, 0.20, 0.17 and 0.03, respectively. Current knowledge of the emanation processes was also summarized to discuss their affected factors.

Elevation of Glutathione Induced by Low-Dose Gamma Rays and its Involvement in Increased Natural Killer Activity

Abstract Kojima, S., Ishida, H., Takahashi, M. and Yamaoka, K. Elevation of Glutathione Induced by Low-Dose Gamma Rays and its Involvement in Increased Natural Killer Activity. Radiat. Res. 157, 275 – 280 (2002). We examined the relationship between the induction of an increase in the level of glutathione and the elevation of natural killer (NK) activity in mouse splenocytes by a low dose of γ rays. The glutathione levels in mouse splenocytes increased significantly between 2 h and 6 h after whole-body γ irradiation at 0.5 Gy, peaked at 4 h, and then decreased almost to the level before irradiation by 12 h postirradiation. A significant enhancement of NK activity was found in the splenocytes obtained from whole-body-irradiated mice between 4 and 6 h postirradiation. Reduced glutathione (GSH) added exogenously to splenocytes obtained from normal mice enhanced both the total cellular glutathione content and the NK activity in a dose-dependent manner. Other precursors of de novo GSH synthesis, such as cysteine, N-acetylcysteine and oxidized glutathione, also increased the activity. These enhancements were completely blocked by buthionine sulfoximine, an inhibitor of de novo GSH synthesis. We conclude that the induction of endogenous glutathione in living cells immediately after low-dose γ irradiation is at least partially responsible for the appearance of enhanced NK activity.

Elevation of antioxidant potency in the brain of mice by low-dose γ-ray irradiation and its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage

The elevation of endogenous thiol-related antioxidants and free radical scavenging enzymes in the brain of C57BL/6 female mice after low-dose gamma-ray irradiation and its inhibitory effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage were investigated. The brain level of the reduced form of glutathione (GSH) increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at 3 h post-treatment, and remained elevated until 12 h. Thioredoxin (TRX) was also transiently increased after irradiation. The activities of free radical scavenging enzymes, including Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, were significantly induced after irradiation as well. Cerebral malondialdehyde was remarkably elevated by MPTP treatment, and this elevation was suppressed by pre-irradiation (50 cGy). The contents of GSH and TRX were significantly decreased by MPTP treatment in comparison with those of the control group. These reductions both seemed to be attenuated by pre-irradiation with gamma-rays. These results suggest that low-dose gamma-ray irradiation induces endogenous antioxidative potency in the brain of mice and might be effective for the prevention and/or therapy of various reactive oxygen species-related neurodegenerative disorders, such as Parkinsons disease and Alzheimers disease.

Induction of mRNAs for glutathione synthesis-related proteins in mouse liver by low doses of γ-rays

We examined the elevation of the reduced form of glutathione (GSH)level and the induction of MRNAs for proteins involved in the synthesis and regeneration of GSH in the liver of mice after low-dose gamma-ray irradiation. The liver GSH level increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at around 12 h post-treatment. The mRNA of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for de novo synthesis for GSH, showed a small increase that peaked at 6 h after gamma-ray irradiation at a dose of 50 cGy. Only a small increase in gamma-GCS activity was observed throughout the 24-h post-irradiation period. In the case of glutathione reductase (GR), which is involved in the regeneration of GSH from the oxidized form (GSSG), the mRNA level peaked strongly at 1 h, while the activity peaked at twice the control level 12 h after irradiation. The level of mRNA for thioredoxin (TRX), which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked at 1 h and declined thereafter, while the activity peaked at 3 h and then declined sharply. These results indicate that the increase in endogenous GSH immediately following low-dose gamma-ray irradiation is predominantly due to operation of the regeneration cycle and not de novo synthesis. We also examined the dependence of mRNA induction on the gamma-ray dose.

Change of glutathione peroxidase synthesis along with that of superoxide dismutase synthesis in mice spleens after low-dose X-ray irradiation

We have previously demonstrated that the activity of superoxide dismutase (SOD), an antioxidant, is enhanced by low-dose X-ray irradiation in various organs of animals such as rats. Since SOD is an enzyme that mediates the dismutation of O2- to H2O2, the question as to whether the resultant H2O2 is further detoxicated into H2O and O2 or not must still be evaluated. Hence, we studied the effect of low-dose X-ray irradiation on the synthesis of glutathione peroxidase (GSHPx), which is an antioxidant that catalyzes this reaction. The results suggest that H2O2 produced by increased SOD activity can be detoxicated into H2O and O2 due to simultaneous enhancement of the GSHPx activity by X-ray irradiation at 20 cGy, in contrast to irradiation at 400 cGy. The results also show the enhancement in enzyme activities by induction of their synthesis shortly after irradiation at 20 cGy. Moreover, as this phenomenon was observed in BALB/c mice (which are more radiation-sensitive compared to other mouse strains) and radiation-resistant C57BL/6NJcl mice, it was considered to be a common phenomenon in the rat spleen.

Prevention of Type I Diabetes by Low-Dose Gamma Irradiation in NOD Mice

Abstract Takahashi, M., Kojima, S., Yamaoka, K. and Niki, E. Prevention of Type I Diabetes by Low-Dose Gamma Irradiation in NOD Mice. Pretreatment with nonlethal, low-dose irradiation has been shown to have a protective effect against oxidative injury in animal tissues. Since oxidative injury of tissues is known to be a major cause of many human diseases, we examined the effect of low-dose irradiation on the progression of type I diabetes in mice. Nonobese diabetic (NOD) mice were treated with γ irradiation and the progression of the disease was monitored. An elevated level of glucose in urine was first detected at 15 weeks of age in the control NOD mice, whereas the detection was delayed as long as 7 weeks when the mice received a single dose of 0.5 Gy total-body irradiation between 12 and 14 weeks of age. The greatest effect was observed in the mice irradiated at 13 weeks of age. The increase in blood glucose and decrease in blood insulin were effectively suppressed by irradiation at 13 weeks of age. Both suppression of cell death by apoptosis and an increase in superoxide dismutase (SOD) activity were observed in the pancreas 1 week after irradiation. The results indicate that treatment with 0.5 Gy γ rays suppresses progression of type I diabetes in NOD mice. This is the first report on the preventive effect of low-dose irradiation on disease progression.

Low-dose γ-ray irradiation reduces oxidative damage induced by CCl4 in mouse liver

Abstract We examined the effects of irradiation (50 cGy of γ-ray) reducing the oxidative damage in carbon tetrachloride (CCl4)-hepatopathy mice. We made pathological examinations and analyzed transaminase activity (glutamic oxaloacetic transaminase and glutamic pyruvic transaminase), lipid peroxide level and the activities of endogenous antioxidants in the mouse. The irradiation was found to accelerate the recovery. Based on pathological examination as well as changes in each transaminase activity and lipid peroxide levels, it was shown that hepatopathy improved 3 d after the irradiation. The activities of glutathione reductase and glutathione peroxidase rapidly elevated after irradiation, and the total glutathione content gradually increased in the irradiation group. Both activities of γ-glutamylcysteine synthetase and catalase were higher than normal at all times after the irradiation and gradually increased. In addition, the γ-glutamylcysteine synthetase activity changed in a similar fashion to the total glutathione content. However, superoxide dismutase activity in both groups decreased and that of the irradiation group was significantly lower than that of the sham-irradiation group. These findings suggest that low-dose radiation relieved functional disorder at least in the liver of mice with active oxygen diseases.

Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays

First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso-hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose gamma-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of gamma-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose gamma-ray irradiation. The level of mRNA for gamma-glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. gamma-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose gamma-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.

Possible role of elevation of glutathione in the acquisition of enhanced proliferation of mouse splenocytes exposed to small-dose γ-rays

PURPOSE To examine the relation between the induction of an increased glutathione level and the elevated proliferative response of mouse splenocytes by a small dose of gamma-rays. MATERIALS AND METHODS Male ICR strain mice, 7 weeks of age, were divided into irradiated and non-irradiated control groups. Irradiation was done with gamma-rays from a 137Cs source at a dose of 50 cGy (1.11 Gy/min). Glutathione content in the splenocytes was measured using a modified spectrophotometric technique. Concanavalin A (Con A)-induced proliferative response of the splenocytes after whole-body gamma-ray irradiation was estimated from the 3H-thymidine incorporation into the cells. RESULTS The glutathione level in mouse splenocytes increased 2 h after whole-body y-ray irradiation at 50cGy, peaked at 4h and thereafter decreased almost to the zero-time level by 12-h postirradiation. A significant enhancement of Con A-induced proliferation was observed in the splenocytes obtained from the whole-body-irradiated animals between 2h and 6h post-irradiation. Glutathione exogenously added to splenocytes obtained from normal mice enhanced the Con A-induced proliferation of splenocytes in a dose-dependent manner. This enhancement was completely blocked by buthionine sulfoximine, a specific inhibitor of the de novo pathway of glutathione synthesis. CONCLUSIONS The induction of endogenous glutathione immediately after low-dose gamma-ray irradiation is at least partially responsible for the enhancement of immune function, and may throw light on the mechanisms of carcinostatic effects induced by low dose ionizing radiation.Purpose : To examine the relation between the induction of an increased glutathione level and the elevated proliferative response of mouse splenocytes by a small dose of γ-rays. Materials and methods : Male ICR strain mice, 7 weeks of age, were divided into irradiated and non-irradiated control groups. Irradiation was done with γ-rays from a 137 Cs source at a dose of 50cGy (1.11Gy/min). Glutathione content in the splenocytes was measured using a modified spectrophotometric technique. Concanavalin A (Con A)-induced proliferative response of the splenocytes after whole-body γ-ray irradiation was estimated from the 3 H-thymidine incorporation into the cells. Results : The glutathione level in mouse splenocytes increased 2h after whole-body γ-ray irradiation at 50 cGy, peaked at 4h and thereafter decreased almost to the zero-time level by 12-h postirradiation. A significant enhancement of Con A-induced proliferation was observed in the splenocytes obtained from the wholebody-irradiated animals between 2h and 6h post-irradiation. Glutathione exogenously added to splenocytes obtained from normal mice enhanced the Con A-induced proliferation of splenocytes in a dose-dependent manner. This enhancement was completely blocked by buthionine sulfoximine, a specific inhibitor of the de novo pathway of glutathione synthesis. Conclusions : The induction of endogenous glutathione immediately after low-dose γ-ray irradiation is at least partially responsible for the enhancement of immune function, and may throw light on the mechanisms of carcinostatic effects induced by low dose ionizing radiation.