低線量放射線による抗酸化系の誘導と活性酸素病治療への応用の可能性

We clarified that adequate oxygen stress induced by low dose radiation activates not only chemical biological protective function, such as induction of the synthesis of SOD, GPX and HSP70, but also the biomembrane function, such as enhanced membrane fluidity and ATPase activity. It is possible that activation of these mechanisms alleviates in vivo oxidation injuries resulting in alleviation of pathologic condition, such as symptoms of hepatopathy and diabetes mellitus. Namely, adequate activation of the functions of the living body by low dose radiation can contribute to suppressing aging and to preventing or reducing active oxygen species related diseases which are thought to involve peroxidation and have been regarded as the diseases for which radon spring water is an effective treatment. Clarification in detail of the mechanisms of these phenomena is required to understand the effects of low dose radiation on the functions of the living body, including adaptive response.ストレスなどの原因により生体内に生じた過剰な活性酸素は毒性を有し，これが細胞や組織障害につながり，老化や発癌など種々の病的状態を生み出している。これに対し，生体には活性酸素を消去したり，損傷を起こした分子を修復したりして結果的に生ずる障害を防御する機構がある。この抗酸化系防御機構は適度な酸化ストレス，即ち少量の活性酸素を生体内に発生させる環境下では，逆に活性化する可能性があり，注目されている。本総説は，少量活性酸素を生体内に生じさせる低線量放射線による抗酸化系防御機構の活性化の有無，生体膜の構造変化と機能活性に及ぼす作用，活性酸素病などの遠因となる生体内酸化傷害に及ぼす作用，さらにはラドン（主にα線放出）療法の適応症の機構について，今までに実施した我々の研究例を中心に総括し，評価するものである。即ち，マウス，ラットへのX線γ線照射実験やラビットへのラドン吸入実験により得られた成果例は次の通りである。低線量のX線，γ線照射やラドン吸入により，高線量放射線の場合とは逆に，週齢や臓器などに放射線感受性に違いはあるものの過酸化脂質量が減少し，膜流動性やATPase活性が若齢値に近づくように変化した。SOD，Cat，GPXなどの酵素活性が誘導合成に伴い亢進した。また，低線量放射線照射によりI型糖尿病症状，鉄あるいは四塩化炭素の誘導による肝障害，MPTPの誘導による脳障害などが緩和された。さらに，ラドン吸入により組織循環の促進や疼痛の緩和などが明らかになった。これらの知見より，低線量放射線は抗酸化系防御機構を活性化するとともに生体膜機能の若返り化を導くことが示唆できた。また，低線量放射線は糖尿病I型症状や肝，脳障害を緩和することから，活性酸素病の治療応用への可能性も示唆できた。さらに，ラドン療法の適応症の代表例である疼痛緩和などについても機構解明の一端がなされた

Activation of Biodefense System by Low-Dose Irradiation or Radon Inhalation and Its Applicable Possibility for Treatment of Diabetes and Hepatopathy

Adequate oxygen stress induced by low-dose irradiation activates biodefense system, such as induction of the synthesis of superoxide dismutase (SOD) and glutathione peroxidase. We studied the possibility for alleviation of oxidative damage, such as diabetes and nonalcoholic liver disease. Results show that low-dose γ-irradiation increases SOD activity and protects against alloxan diabetes. Prior or post-low-dose X- or γ-irradiation increases antioxidative functions in livers and inhibits ferric nitrilotriacetate and carbon tetrachloride-induced (CCl4) hepatopathy. Moreover, radon inhalation also inhibits CCl4-induced hepatopathy. It is highly possible that low-dose irradiation including radon inhalation activates the biodefence systems and, therefore, contributes to preventing or reducing reactive oxygen species-related diabetes and nonalcoholic liver disease, which are thought to involve peroxidation

Recent medical studies on radon therapy in Europe

本総説は,本邦で実施している三朝ラドン温泉の適応症に関する機構解明に資するために調査した欧州におけるラドン療法の医学的研究に関する最近の動向の概要についてまとめたものである｡すなわち,ラドンを用いた温泉や坑道での療法の適応症には,脊椎の非細菌性炎症(べヒテレフ病),慢性多発性関節炎,気管支喘息などが含まれる｡臨床医学的研究として,以前,客観的方法で検討されたものはほとんどなかったが,最近,無作為化二重盲検臨床試験などにより,ラドン療法がベヒテレフ病,慢性多発性関節炎などの患者の痛みを緩和させる効能があることが実証されつつある｡また,基礎医学的研究として,抗酸化機能や免疫機能などの指標に着目した動物実験により,ラドン療法の機構を解明する上で合理的根拠が得られつつあることもわかった｡さらに,これらの知見と本邦での研究動向を踏まえ,今後,期待されるラドン療法の機構解明を行うための研究課題を提案した｡To elucidate the mechanism of radon therapy in Misasa radon spa, the author researched these recent studies in Europe. Parts of the results were as follows. In spas and galleries with a slightly elevated radon activity, the empirical medicine showed the same indications in the world. It mainly includes the more painful rheumatic diseases such as deformation or degeneration of the joints and non bacterial inflammation of muscles, tendons or joints ; Morbus Bechterew and other diseases of the vertebral column like spondylarthrosis or osteochondrosis. While these effects were seldom documented in an objecive manner formly, in recent years several prospective randomized double-blind studies proved the pain reducing efficacy of radon therapy in patients with cervical pain syndromes, with chronic polyarthritis or with Morbus Bechterew. Studies in experimental animal models have accumulated remarkable data in cultured cells, organs and tissue that provide a rationale to explain the observed effects of radon therapy in patients

An Assessment of Radioactivity Levels of 210Pb and 40K in Tobacco and Radiation Exposure from Smoking

No research has been conducted on the radiation influence of tobacco on the alimentary system, although there have been some previous works on the respiratory system. In this study, the radioactive concentrations of 210Pb and 40K in a cigarette sample were first measured. The transfer factors of the nuclides from tobacco into smoke and solution (saliva and/or alcohol) were then examined. Moreover, the radiation doses from smoke inhalation were also evaluated. The radioactive concentrations of 210Pb and 40K in the cigarette tobacco were 0.01 and 0.3 Bq/cigarette. Since this 210Pb activity and the 210Po activity previously reported for the same sample were comparable, it can be concluded that there was a radioactive equilibrium between the 2 nuclides. The observed transfer factor of 210Pb (12%) into smoke was almost the same as that of 40K (15%), whereas the reported value for 210Po (60%) was significantly higher. The radiation doses due to inhalation of cigarette smoke varied from organ to organ, depending on the organotropic properties of the nuclide. For example, the kidneys, respiratory tract, and spleen showed relatively high doses from 210Pb and 210Po. The leaching rates indicated an inconsistent tendency related to solution types. This result could suggest that alcohol drinking, which is common in smokers, does not especially enhance the leaching characteristics

Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol- induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol- induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol- induced hepatopathy in mice

Inhibitory Effects of Prior Low-dose X-irradiation on Cold-induced Brain Injury in Mouse

We examined the inhibitory effects of low-dose X-irradiation on mouse brain tissue with cold-induced injury by comparing tissue samples from three groups of mice: control, sham-irradiated cold-exposed, and X-ray-irradiated (0.5 Gy) cold-exposed mice. The water content in brain increased significantly in the sham-irradiated group following the cold-induced injury relative to the control group. However, water content in brain tissue from the X-ray-irradiated group was significantly lower than that from the sham-irradiated group. Levels of antioxidants, such as superoxide dismutase and glutathione, in brain tissue from the X-ray-irradiated group were higher than those from the sham-irradiated group. Moreover, the cold injury-induced cell death, particularly apoptosis, while low-dose irradiation inhibited cell death, especially among glial cells, but not numeral cells. These findings suggest that prior low-dose X-irradiation activated antioxidant function and inhibited cold-induced brain injury

Recent trend of research on the adaptive response induced by low dose radiation and its significance

本総説は,低線量放射線に対する生体の適応応答(以下,適応応答)に関してその効果を含む最近の研究動向,さらに放射線防護との関係についてまとめたものである｡特にこの分野で最も検討が進んでいる｢低線量放射線照射の生物学的影響｣に関する国際研究組織(BELLE)での動向を中心に報告するものである｡即ち,ヒトと自然放射線との共存などヒトの生活環境と適応応答について,適応応答の短期的･長期的効果など適応応答の効果とその生物学的意義について言及した｡次に,適応応答の医療などへの応用の可能性について,また,適応応答と放射線防護との関係についても言及した｡ここで,低線量放射線にはヒトへの有益な効果があるとの多くの報告例がある半面,放射線防護の面では微量放射線でも危険とする考え方がその根拠にあることがわかった｡このため,今後は更なる低線量放射線の生体影響研究を進めるとともに,両者の間の隙間をなくす現実的･合理的な対応が求められている｡We reviewed the recent trend of research on the adaptive response induced by low dose radiation and its significance. The following view were obtained. Risk assessment is fundamental to the protection of public health from radiation exposure, but any estimate of risk is subject to numerous major uncertainties. In view of the uncertainties surrounding the shape of dose-response curves at low doses of ionizing radiation. the linear nonthreshold dose-response model is now widely accepted as a paradigm in radiation protection practice and risk analysis. However, interest among scientists in obtaining a more conclusive understanding of the effects of low dose radiation has been evident in recent initiatives, such as adaptive response of low dose radiation, in part to help verify or disprove the linear model. A vigorous worldwide effort is now apparently underway to understand the basic mechanisms underlying the biological effects of low dose radiation. This review presents a series of papers representing the progress going on, which will undoubtably make an important contribution to this field of research

Spa therapy for patients with respiratory disease. Clinical efficacy and action mechanisms of the therapy on asthma

呼吸器疾患に対する温泉療法は,最近の22年間にわたり行われてきた結果,その有用性は十分明かとなっている｡この22年の間に,温泉療法を受ける対象もかなり変わってきており,例えば気管支喘息では,ステロイド依存性重症難治性喘息の全症例に対する割合は明 らかに低くなってきている｡また,COPDでは最近全症例に対する肺気腫の割合も,また症例数も著明に増加しつつある｡一方,温泉療法を求めて来院される症例数は年ごとに増加する傾向にあり,初期の5年間と比べ,最近の5年間では,気管支喘息では8.2倍,また肺気腫では 34.8倍の増加が観察されている｡呼吸器疾患に対する温泉療法の作用機序としては,直接作用として,自･他覚症状の改善,換気機能の改善,気道過敏性の改善,気道抵抗の低下,肺の過膨脹の改善,過分泌の抑制などが観察される｡一方,間接作用としては,副腎皮質機能の改善,精神的リラックス,抗酸化酵素であるSOD活性の克進などが観察され,これらの間接作用も気管支喘息の病態改善に重要な役割を果しているものと考えられる｡Spa therapy which has been performed for patients with respiratory disease, particularly for those with asthma and pulmonary emphysema for last 22 years demonstrates that spa therapy is effective for asthma and pulmonary emphysema. The characteristics of patients with respiratory disease has been changing during last 22 years : the frequency of patients with steroid-dependent intractable asthma (SDIA) tends to decrease inspite of an increase in number of those with asthma who has been admitted at Misasa Medical Center for spa therapy. The frequency and number of patients with pulmonary emphysema has been increasing in recent years. Spa therapy has direct action mechanism for airways such as improvement of subjective and objective symptoms, and improvement of ventilatory function, bronchial hyperresponsiveness, and hyperinflation of the lungs. The therapy has also indirect action mechanism for other organs excluding the airways such as improvement of suppressed function of adrenocortical glands, psychological relaxation, and an increase in SOD activity. These indirect actions of spa therapy play an important role in treatment of the disease

Inhibitory Effects of Pre and Post Radon Inhalation on Carbon Tetrachloride-induced Oxidative Damage in Mouse Organs

Radon inhalation activates antioxidative functions in some organs of mice. We examined the prevention effects of pre radon inhalation and the alleviation effects of post radon inhalation on carbon tetrachloride (CCl4)-induced oxidative damage in the brain, heart, lung, liver, and kidney of mice. In addition, we compared the effect of pre and post radon inhalation on oxidative damage. Mice inhaled radon at a concentration of 18000Bq/m3 for 6hrs before or after CCl4 administration. As a result, the total glutathione(t-GSH) contents and catalase(CAT) activities in the brain, heart, lung, liver, and kidney and superoxide dismutase(SOD) activities in the heart and lung were significantly higher in pre and post radon-inhaled mice than in mice treated with only CCl4. Pre radon inhalation inhibited and post radon inhalation reduced lipid peroxidation induced by CCl4. In addition, there were no significant differences in lipid peroxide(LPO) levels in the brain, heart, lung, liver, and kidney between pre and post radon-inhaled mice. These findings suggested that post radon inhalation has the same effects as pre radon inhalation against CCl4-induced oxidative damage in the brain, heart, lung, liver, and kidney

Basic study on the effects of the archeological investigation and the construction work on the environmental radiation

In this paper, we investigated how the excavation of ruins and the construction work affected the environmental radiation in the Shikata campus of Okayama University (S-campus). The environmental radiation was steady in the S-campus until 1997, but began to change since 1998, while the ruin's survey and the construction work started frequently after 1998 in the S-campus. In general, the soil and the concrete include the natural radioisotope (uranium series and thorium series, etc). When ruins are surveyed, it is necessary to move a large amount of the soil. In addition, a large amount of the concrete is used for the construction work. To measure the environmental radiation, the monitor posts were set up on the east and west sides of the building of the Radioisotope Center (RIC). We sampled the soil in the container in each place. We used the high-purity germanium detector to analyze them. The monitor posts showed the difference in the in-air dose rate in each place in the S-campus. The in-air dose rate at the east side of the RIC was higher than that at the west side. The result of analysis showed that the soil includes the (40)K at the east side. While the specific activity of the 40K was 0.849Bq/g at the east side, the (40)K was hardly detected in the soil at the west side. The each soil included the 214-lead and 214-bismus ((214)Pb, (214)Bi), however, there was no significant difference in the specific activity of the each soil. The concrete included (40)K, whose specific activity was 0.492Bq/g. It was suggested that the change of the environmental radiation was attributed to radon and its daughter nuclides in the soil rather than the radiation from the concrete in the buildings