Katsumi Hanamoto

Physiologically Based Pharmacokinetic Modeling of Inhaled Radon to Calculate Absorbed Doses in Mice, Rats, and Humans

This is the first report to provide radiation doses, arising from inhalation of radon itself, in mice and rats. To quantify absorbed doses to organs and tissues in mice, rats, and humans, we computed the behavior of inhaled radon in their bodies on the basis of a physiologically based pharmacokinetic (PBPK) model. It was assumed that radon dissolved in blood entering the gas exchange compartment is transported to any tissue by the blood circulation to be instantaneously distributed according to a tissue/blood partition coefficient. The calculated concentrations of radon in the adipose tissue and red bone marrow following its inhalation were much higher than those in the others, because of the higher partition coefficients. Compared with a previous experimental data for rats and model calculation for humans, the present calculation was proved to be valid. Absorbed dose rates to organs and tissues were estimated to be within the range of 0.04–1.4 nGy (Bqm−3)−1 day−1 for all the species. Although the dose rates are not so high, it may be better to pay attention to the dose to the red bone marrow from the perspective of radiation protection. For more accurate dose assessment, it is necessary to update tissue/blood partition coefficients of radon that strongly govern the result of the PBPK modeling.

Radioactivity and radon emanation fraction of the granites sampled at Misasa and Badgastein

The chemical composition was analyzed and the radioactivity, radon exhalation rate and emanation fraction were measured to investigate the characteristics of the granites sampled at Misasa and Badgastein, world famous for radon therapy. The Misasa granite was probably composed of quartz, albite and microcline. The Badgastein granite was probably composed of quartz and muscovite. The radon exhalation rates and emanation fractions of the Misasa granite were much higher than those of the Badgastein granite, regardless of the (226)Ra activity concentrations.

Differences of natural radioactivity and radon emanation fraction among constituent minerals of rock or soil

We examined differences in the radioactive characteristics among the main minerals forming granite materials. Using a non-toxic high-density agent, minerals were separated from rock (granite-gneiss) and soil (weathered granite) samples. The natural radioactivity ((238)U and (226)Ra) and radon emanation fraction of the minerals were then studied by gamma-ray spectrometry. The radon emanation fractions (27-43%) of the minerals from the soil were much higher than those (0.6-4.6%) of the rock minerals. Additionally, the emanation fractions differed greatly among the minerals separated from both the bulk rock and soil. These results were discussed in terms of the differences of surface area and radium distribution in the mineral grains. It was noticeable that a higher emanation fraction than expected for quartz was commonly observed in the rock and soil samples. We then estimated the contribution of each constituent mineral to the total radon exhalation from the bulk samples. The result depended not only on the radon emanation fraction, but also on the (226)Ra activity and the mineral content. Furthermore, using the obtained data, we also discussed the effect of grain size on radon emanation and why this has been reported to vary markedly in previous studies.

First model of the effect of grain size on radon emanation

The present model represents an improvement on previous models of radon emanation from soil by incorporating soil grain size in addition to moisture. Monte Carlo simulation was employed in the calculation since it was difficult to mathematically express the radon emanation fraction for the present soil model. Grain size is one of the most important factors in describing the properties of soil. Grain size was demonstrated to affect the radon emanation fraction, depending on moisture content. Although the emanation fraction is generally considered to be proportional to grain size, the result of the model calculation suggested that the effect of grain size is not so simple. This study should serve as an initial step toward improving the modeling of this radon emanation.

Development of a phantom compatible for MRI and hyperthermia using carrageenan gel—relationship between T1 and T2 values and NaCl concentration

The authors developed a phantom, designated as the CAGN phantom, compatible for MRI and hyperthermia that is useful in the fundamental studies of non-invasive MR thermometry. The ingredients of this phantom are carrageenan, GdCl3 as a T1 modifier, agarose as a T2 modifier, NaCl as a conductivity modifier, NaN3 as an antiseptic and distilled water. Another phantom that was developed, the CAG phantom, has relaxation times that are adjustable to those of any human tissue. To use this phantom for electromagnetic heating, NaCl was added to change the conductivity of the phantom and clarified the relationship between the conductivity and NaCl concentration. This study examined the relationship between relaxation times and NaCl concentration of the CAGN phantom. The results showed that both T1 and T2 values were affected by NaCl and the experimental results led to the empirical formulae expressing the relationship between the relaxation rates (1/T1, 1/T2) and the concentrations of GdCl3, agarose and NaCl. The appropriate concentrations of T1 and T2 modifiers were calculated from these empirical formulae when making a specified phantom that has the required relaxation times and NaCl concentration.

Comparative study on the inhibitory effects of α-tocopherol and radon on carbon tetrachloride-induced renal damage.

Since the 2011 nuclear accident in Fukushima, the effects of low-dose irradiation, especially internal exposure, are at the forefront of everyone’s attention. However, low-dose radiation induced various stimulating effects such as activation of antioxidative and immune functions. In this study, we attempted to evaluate the quantitative effects of the activation of antioxidative activities in kidney induced by radon inhalation on carbon tetrachloride (CCl4)-induced renal damage. Mice were subjected to intraperitoneal (i.p.) injection of CCl4 after inhaling approximately 1000 or 2000 Bq/m3 radon for 24 h, or immediately after i.p. injection of α-tocopherol (100, 300, or 500 mg/kg bodyweight). In case of renal function, radon inhalation at a concentration of 2000 Bq/m3 has the inhibitory effects similar to α-tocopherol treatment at a dose of 300–500 mg/kg bodyweight. The activities of superoxide dismutase and catalase in kidneys were significantly higher in mice exposed to radon as compared to mice treated with CCl4 alone. These findings suggest that radon inhalation has an antioxidative effect against CCl4-induced renal damage similar to the antioxidative effects of α-tocopherol due to induction of antioxidative functions.

Radioactivity of 210Pb in Japanese cigarettes and radiation dose from smoking inhalation.

It is well known that cigarette tobaccos contain naturally occurring radioactive nuclides such as (210)Pb and (210)Po. In many countries, the radioactivity of tobaccos has been measured to estimate the effective dose from smoking inhalation. The present study covered 24 cigarette brands including the top 20 of sales in Japan between April 2008 and March 2009. The activity concentrations of (210)Pb were measured by gamma-ray spectrometry, and then those of its progeny ((210)Po) were evaluated assuming the radioactive equilibrium between the two nuclides. Their concentrations were in the range of 2-14 mBq cigarette(-1) with an arithmetic mean of 8±3 mBq cigarette(-1). The annual committed effective doses were also calculated, based on the scenario that a smoker consumes 20 cigarettes a day. The average doses from (210)Pb and (210)Po inhalations were 22±9 and 68±27 μSv y(-1), respectively.

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

Evaluating the protective effects of radon inhalation or ascorbic acid treatment after transient global cerebral ischemic injury in gerbils

ABSTRACT In this study, we compared the protective effects of radon inhalation and ascorbic acid administration on transient global cerebral ischemic injury in gerbils. Gerbils were treated with radon inhalation (2000 Bq/m3, 24 hours) or ascorbic acid (100, 300, or 500 mg/kg body weight). Then, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that the number of damaged neurons was significantly increased in gerbils that underwent ischemia compared with that in control gerbils. However, the number of damaged neurons in gerbils treated with radon or 500 mg/kg of ascorbic acid before ischemia was significantly lower than gerbils who were subjected to ischemia without any pretreatment, and the protective effects of radon inhalation were similar to the effects of administering 500 mg/kg ascorbic acid. The levels of superoxide dismutase (SOD) and total glutathione (t-GSH) in brain tissue were increased to a similar extent by pretreatment with radon inhalation or 500 mg/kg of ascorbic acid. These findings suggested that radon inhalation has a protective antioxidative effect against transient global cerebral ischemic injury similar to 500 mg/kg ascorbic acid treatment.

Activation of Antioxidative Functions by Radon Inhalation Enhances the Mitigation Effects of Pregabalin on Chronic Constriction Injury-Induced Neuropathic Pain in Mice

Radon inhalation brings pain relief for chronic constriction injury- (CCI-) induced neuropathic pain in mice due to the activation of antioxidative functions, which is different from the mechanism of the pregabalin effect. In this study, we assessed whether a combination of radon inhalation and pregabalin administration is more effective against neuropathic pain than radon or pregabalin only. Mice were treated with inhaled radon at a concentration of 1,000 Bq/m3 for 24 hours and pregabalin administration after CCI surgery. In mice treated with pregabalin at a dose of 3 mg/kg weight, the 50% paw withdrawal threshold of mice treated with pregabalin or radon and pregabalin was significantly increased, suggesting pain relief. The therapeutic effects of radon inhalation or the combined effects of radon and pregabalin (3 mg/kg weight) were almost equivalent to treatment with pregabalin at a dose of 1.4 mg/kg weight or 4.1 mg/kg weight, respectively. Radon inhalation and the combination of radon and pregabalin increased antioxidant associated substances in the paw. The antioxidant substances increased much more in radon inhalation than in pregabalin administration. These findings suggested that the activation of antioxidative functions by radon inhalation enhances the pain relief of pregabalin and that this combined effect is probably an additive effect.