Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan.

No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants' bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis.

Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice.

The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate γ-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range.

Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice.

Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m3 radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury.

Changes in Sulfur Metabolism in Mouse Brains following Radon Inhalation.

Therapy using hot springs, including the high-level radioactive gas "radon", is traditionally conducted as an alternative treatment for various diseases. Oxidative-stress-related diseases are inhibited by the enhancement of antioxidative functions following radon inhalation. We have reported that radon inhalation increased the level of anti-oxidants, such as glutathione (G-SH), in the brain and had a protective antioxidative effect against transient global cerebral ischemic injury. However, no studies have yet revealed the changes in G-SH associated substances after radon inhalation. In this study, we comprehensively analyzed several metabolites, focusing on G-SH. Mice were exposed to radon at concentrations of 200, 2000, or 20,000 Bq/m3 for 1, 3, or 10 days. We detected 27 metabolites in the mouse brains. The result showed that the L-methionine levels increased, whereas the levels of urea, glutathione, and sulfite ion decreased under any condition. Although the ratio of G-SH to oxidized glutathione (GS-SG) decreased, glutathione monosulfide (G-S-SH) and cysteine monosulfide (Cys-S-SH) increased after radon inhalation. G-S-SH and Cys-S-SH can produce a biological defense against the imbalance of the redox state at very low-dose irradiation following radon inhalation because they are strong scavengers of reactive oxygen species. Additionally, we performed an overall assessment of high-dimensional data and showed some specific characteristics. We showed the changes in metabolites after radon inhalation using partial least squares-discriminant analysis and self-organizing maps. The results showed the health effects of radon, especially the state of sulfur-related metabolites in mouse brains under the exposure conditions for radon therapy.

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice.

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m3 and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m3 thoron inhalation was lower than that after 500 Bq/m3 thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m3 and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m3 was more effective than that at 2000 Bq/m3, possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m3 and AA administration promoted an early recovery from alcohol-induced liver damage.

Radon Solubility and Diffusion in the Skin Surface Layer.

In specific situations such as bathing in a radon spa, where the radon activity concentration in thermal water is far higher than that in air, it has been revealed that radon uptake via skin can occur and should be considered for more precise dose evaluation. The primary aim of the present study was to numerically demonstrate the distribution as well as the degree of diffusion of radon in the skin, with a focus on its surface layer (i.e., stratum corneum). We developed a biokinetic model that included diffusion theory at the stratum corneum, and measured radon solubility in that tissue layer as a crucial parameter. The implementation of the model suggested that the diffusion coefficient in the stratum corneum was as low as general radon-proof sheets. After a 20-min immersion in water, the simulated depth profile of radon in the skin showed that the radon activity concentration at the top surface skin layer was approximately 103 times higher than that at the viable skin layer. The information on the position of radon as a radiation source would contribute to special dose evaluation where specific target cell layers are assumed for the skin.

A simple method for estimating the potential of the pyroelectric crystal surface.

The potential of the pyroelectric crystal surface has been estimated using experimental data. The temperature of the pyroelectric crystal, the electron current from the crystal surface to the target, and the X-ray spectrum were simultaneously measured. The potential calculated from the temperature and the electron current was compared with the experimental endpoint energy of the X-ray spectrum. The calculated potential reasonably agreed with the experimental endpoint energy.

Confirmation of efficacy, elucidation of mechanism, and new search for indications of radon therapy.

Indications of radon therapy include various diseases related to respiratory, painful, digestive, chronic degenerative, senile, etc. derived from reactive oxygen species, but most are based on empirical prescriptions. For this reason, we have evaluated the relation between the biological response caused by radon and the tissue/organ absorbed dose more quantitatively, and have promoted the elucidation of mechanisms related to the indication and searching newly. As a result, as a mechanism, a series of moderate physiological stimulative effects accompanying a small amount of oxidative stress by radon inhalation are being elucidated. That is, hyperfunction of anti-oxidation/immune regulation/damage repair, promotion of anti-inflammation/circulating metabolism/hormone secretion, induction of apoptosis/heat shock protein, etc. Also, new indications include inflammatory/neuropathic pain, hepatic/renal injury, colitis, type 1 diabetes, complication kidney injury, hyperuricemia, transient cerebral ischemia, and inflammatory edema. Furthermore, we examined the combined antioxidant effect of radon inhalation and antioxidants or therapeutic agents. As a result, it was clear that any combination treatment could enhance the suppression effect of disease. It can be expected that radon therapy can be used effectively by applying it in addition to usual treatment, since reduction in its dosage can also be expected by concomitant use for drugs with strong side effects.

Mechanisms of action of radon therapy on cytokine levels in normal mice and rheumatoid arthritis mouse model.

The typical indication of radon therapy is rheumatoid arthritis. Although there are several reports that radon therapy has regulation effects on Th17 cells, there has been no study reporting that radon inhalation affects the immune balance among Th1, Th2, and Th17. The purpose of this study is to examine the cytokine changes after radon inhalation. BALB/c mice inhaled radon at 2,000 Bq/m3 for 2 or 4 weeks. SKG/Jcl mice inhaled radon at 2,000 Bq/m3 for 4 weeks after zymosan administration. The results showed that radon inhalation for 4 weeks activated the immune response of Th1, Th2, and Th17. Moreover, the balance among them was not lost by radon inhalation. Radon inhalation for 4 weeks decreased superoxide dismutase activity and increased catalase activity in spleen. These findings suggest that an imbalance of oxidative stress may contribute to activate the immune response. Although zymosan administration activated Th17 immune response and decreased Th1 and Th2 immune response in SKG/Jcl mice, most cytokines related to Th1, Th2, and Th17 approached the normal level by radon inhalation. These findings suggested that radon inhalation has a different action between SKG/Jcl mice and normal BABL/c mice. This may indicate that radon inhalation has an immunomodulation function.

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions.

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m3 (for one, three, or 10 days). The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m3 radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m3 radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20-40% (2 kBq/m3 for three days or 20 kBq/m3 for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15-60% and 15-45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage.

Dosimetry of radon progeny deposited on skin in air and thermal water.

It is held that the skin dose from radon progeny is not negligibly small and that introducing cancer is a possible consequence under normal circumstances as there are a number of uncertainties in terms of related parameters such as activity concentrations in air and water, target cells in skin, skin covering materials, and deposition velocities. An interesting proposal has emerged in that skin exposure to natural radon-rich thermal water as part of balneotherapy can produce an immune response to induce beneficial health effects. The goal of this study was to obtain generic dose coefficients with a focus on the radon progeny deposited on the skin in air or water in relation to risk or treatment assessments. We thus first estimated the skin deposition velocities of radon progeny in air and thermal water based on data from the latest human studies. Skin dosimetry was then performed under different assumptions regarding alpha-emitting source position and target cell (i.e. basal cells or Langerhans cells). Furthermore, the impact of the radon progeny deposition on effective doses from all exposure pathways relating to 'radon exposure' was assessed using various possible scenarios. It was found that in both exposure media, effective doses from radon progeny inhalation are one to four orders of magnitude higher than those from the other pathways. In addition, absorbed doses on the skin can be the highest among all pathways when the radon activity concentrations in water are two or more orders of magnitude higher than those in air.

The Effects of Low-Dose-Rate γ-irradiation on Forced Swim Test-Induced Immobility and Oxidative Stress in Mice.

The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function. We evaluated the effects of low-dose γ-irradiation at a low-dose-rate on the FST-induced depletion of antioxidants in mouse organs. Mice received whole-body low-dose-rate (0.6 or 3.0 mGy/h) of low-dose γ-irradiation for 1 week, followed by daily FSTs (5 days). The immobility rate on day 2 compared to day 1 was significantly lower in the 3.0 mGy/h irradiated mice than in sham irradiated mice. The FST significantly decreased the catalase (CAT) activity and total glutathione (t-GSH) content in the brain and kidney, respectively. The superoxide dismutase (SOD) activity and t-GSH content in the liver of the 3.0 mGy/h irradiated mice were significantly lower than those of the non-FST-treated mice. The CAT activity in the lungs of mice exposed to 3.0 mGy/h γ-irradiation was higher than that of non-FST treated mice and mice treated with FST. However, no significant differences were observed in the levels of these antioxidant markers between the sham and irradiated groups except for the CAT activity in lungs. These findings suggest that the effects of low-dose-rate and low-dose γ-irradiation on FST are highly organ-dependent.

Evaluation of the redox state in mouse organs following radon inhalation.

Radon inhalation activates antioxidative functions in mouse organs, thereby contributing to inhibition of oxidative stress-induced damage. However, the specific redox state of each organ after radon inhalation has not been reported. Therefore, in this study, we evaluated the redox state of various organs in mice following radon inhalation at concentrations of 2 or 20 kBq/m3 for 1, 3 or 10 days. Scatter plots were used to evaluate the relationship between antioxidative function and oxidative stress by principal component analysis (PCA) of data from control mice subjected to sham inhalation. The results of principal component (PC) 1 showed that the liver and kidney had high antioxidant capacity; the results of PC2 showed that the brain, pancreas and stomach had low antioxidant capacities and low lipid peroxide (LPO) content, whereas the lungs, heart, small intestine and large intestine had high LPO content but low antioxidant capacities. Furthermore, using the PCA of each obtained cluster, we observed altered correlation coefficients related to glutathione, hydrogen peroxide and LPO for all groups following radon inhalation. Correlation coefficients related to superoxide dismutase in organs with a low antioxidant capacity were also changed. These findings suggested that radon inhalation could alter the redox state in organs; however, its characteristics were dependent on the total antioxidant capacity of the organs as well as the radon concentration and inhalation time. The insights obtained from this study could be useful for developing therapeutic strategies targeting individual organs.

Comparison of antioxidative effects between radon and thoron inhalation in mouse organs.

Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3, and thoron inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron.

X-Irradiation at 0.5 Gy after the forced swim test reduces forced swimming-induced immobility in mice.

The forced swim test (FST) is a screening model for antidepressant activity; it causes immobility and induces oxidative stress. We previously reported that radon inhalation has antidepressant-like effects in mice potentially through the activation of antioxidative functions upon radon inhalation. This study aimed to investigate the effect of prior and post low-dose X-irradiation (0.1, 0.5, 1.0 and 2.0 Gy) on FST-induced immobility and oxidative stress in the mouse brain, and the differences, if any, between the two. Mice received X-irradiation before or after the FST repeatedly for 5 days. In the post-FST-irradiated group, an additional FST was conducted 4 h after the last irradiation. Consequently, animals receiving prior X-irradiation (0.1 Gy) had better mobility outcomes than sham-irradiated mice; however, their levels of lipid peroxide (LPO), an oxidative stress marker, remained unchanged. However, animals that received post-FST X-irradiation (0.5 Gy) had better mobility outcomes and their LPO levels were significantly lower than those of the sham-irradiated mice. The present results indicate that 0.5 Gy X-irradiation after FST inhibits FST-induced immobility and oxidative stress in mice.

Image Quality of the Coronary Angiography with Noise Reduction Technology to Decrease the Radiation Dose.

We examined the effects of a reduced exposure dose on the quality of images from an angiography device augmented with a noise reduction algorithm. Before its clinical application, we compared the diameter of the discrimination limit of the hole with that in the conventional method by a visual evaluation with a contrast-detail (C-D) phantom imaged using the target dose. Based on the results, a reducible dose was determined and applied clinically. The sample population consisted of patients being followed up after percutaneous coronary intervention (PCI) for coronary artery disease; we evaluated the effects of the exposure reduction on image quality. A significant dose reduction was observed by the noise-reduction method compared to the conventional method; the radiation dose to the flat panel detector (FPD) could be reduced to 70 nGy per frame. Clinically, a dose reduction of approx. 40% was obtained while maintaining image quality almost equal to that of the conventional method.

Pressure dependence of X-rays produced by an LiTaO3 single crystal over a wide range of pressure.

The energy spectra of X-rays produced by an LiTaO3 single crystal have been measured at the pressures of 8 × 10-4-4Pa. The energy spectra showed that the endpoint energy steadily increased with decrease of pressure at 2-4Pa and gradually decreased with decrease of pressure at 0.1-2Pa, and became almost constant below 0.1Pa. The amount of X-rays steadily increased with decrease of pressure at 2-4Pa and almost saturated below 0.5Pa. The change of X-rays produced by the LiTaO3 single crystal was compared with the previous works and discussed in relation to the distance between the crystal surface and the target.

Radon inhalation induces manganese-superoxide dismutase in mouse brain via nuclear factor-κB activation.

Although radon inhalation increases superoxide dismutase (SOD) activities in mouse organs, the mechanisms and pathways have not yet been fully clarified. The aim of this study was to determine the details of SOD activation in mouse brain tissue following the inhalation of radon at concentrations of 500 or 2000 Bq/m3 for 24 h. After inhalation, brains were removed quickly for analysis. Radon inhalation increased the manganese (Mn)-SOD level and mitochondrial SOD activity. However, the differences were not significant. There were no changes in the Cu/Zn-SOD level or cytosolic SOD activity. Radon inhalation increased the brain nuclear factor (NF)-κB content, which regulates the induction of Mn-SOD, in the nuclear and cytosolic compartments. The level of inhibitor of nuclear factor κB kinase subunit ß (IKK-ß), which activates NF-κB, was slightly increased by radon inhalation. The expression of cytoplasmic ataxia-telangiectasia mutated kinase in mice inhaling radon at 500 Bq/m3 was 50% higher than in control mice. In addition, NF-κB-inducing kinase was slightly increased after inhaling radon at 2000 Bq/m3. These findings suggest that radon inhalation might induce Mn-SOD protein via NF-κB activation that occurs in response to DNA damage and oxidative stress.

Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice.

Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury.