Masahiro Natsuhori

Detection of DNA damage induced by heavy ion irradiation in the individual cells with comet assay

Investigating the biological effects of high-LET heavy ion irradiation at low fluence is important to evaluate the risk of charged particles. Especially it is important to detect radiation damage induced by the precise number of heavy ions in the individual cells. Thus we studied the relationship between the number of ions traversing the cell and DNA damage produced by the ion irradiation. We applied comet assay to measure the DNA damage in the individual cells. Cells attached on the ion track detector CR-39 were irradiated with ion beams at TIARA, JAERI-Takasaki. After irradiation, the cells were stained with ethidium bromide and the opposite side of the CR-39 was etched. We observed that the heavy ions with higher LET values induced the heavier DNA damage. The result indicated that the amount of DNA damage induced by one particle increased with the LET values of the heavy ions.

PHARMACOKINETICS OF SELENIUM AFTER SODIUM SELENITE ADMINISTRATION TO RATS

Selenium (Se) concentrations in plasma, urine, and feces were determined by PIXE analysis before and after intravenous (iv) / oral (po) administration of sodium selenite (a dose equivalent to 2 mg/kg of selenium) to rats. The concentration-time profiles of Se were analyzed by a pharmacokinetic approach. The plasma Se profile after iv injection was biphasic and well-fit to a 2-compartment open model, showing two half lives (t1/2). The first t1/2 was about 0.3 hr and the second t1/2 was 6.9 hrs. The plasma concentration reached almost basal level after about 80 hrs of injection. On the other hand, plasma profiles after po administration showed absorption rate-limiting elimination. The bioavailability of oral sodium selenite (about 49%) and significantly higher amount of fecal Se excretion indicated relatively poor intestinal absorption of sodium selenite, compared to the previously published data. Urinary Se excretion was almost comparable between iv and po groups. The total recovery of the dose excreted in urine and feces was 30 ± 10 % in iv and 56 ± 15 % in po group. The renal excretion was considered to be a major route of Se excretion after absorption. Significant amount of Se that was not fully excreted was noted, suggesting Se distribution or accumulation in organs, together with volatile excretion.

Study on Dual-Energy X-ray Computed Tomography using Synchrotron Radiation

The electron density is one of the most important elements for the treatment planning in the radiotherapy, because this information is used for the range estimation of the heavy‐ion beam. In order to measure more precise electron density, we have developed the dual‐energy x‐ray CT system using synchrotron radiation. The x‐ray detector consists of 256 × 96 scintillator‐array. It can take more than a hundred projection images per second. The response of the detector to x‐rays was proved to be linear up to at least 1013 photon/pixel. The experiments were carried out using two monochromatic x‐rays of 40 keV and 70 keV at the beam‐line BL20B2 of SPring‐8. As the results from samples of water, ethanol and solutions of dipotassium hydrogenphosphate with five concentrations, the electron densities measured in the dual‐energy x‐ray CT method were in agreement with the theoretical values by about ± 1%. This is almost the same level as that achieved by the one‐dimensional CT system we developed previously. In additi...

TISSUE CONCENTRATION-TIME PROFILE OF SELENIUM AFTER SODIUM SELENITE ADMINISTRATION TO RATS

Selenium (Se) concentration-time profiles in plasma and organs including liver, kidney, heart, lung, spleen and brain of rats (Jcl Wister, 9 wks old, n = 32) were investigated after a single intravenous (iv) / oral (po) administration of sodium selenite (dose is equivalent to 2 mg/kg b.w. of Se), The Se concentration was determined by PIXE analysis. Among the investigated biological samples, Se concentration was the highest in the kidney or liver, followed by the heart, lung or spleen, then plasma, and the brain. Se concentrations in these organs were 0.5 to 5 times of plasma Se. The distribution profiles of Se in the organs were dependent on the route of administration. Furthermore, their profiles appeared almost parallel to the plasma Se-concentration in a logarithmic scale. Compared to the Se concentration-time profiles in plasma and organs by the route of administration, po group showed about 1/4-1/2 of the Se concentration in iv group except for kidney. Kidney kept relatively higher concentration of Se, which was similar in the both groups. This may explain our recently published data that urinary excretion was similar in the both groups. The relative oral bioavailability of plasma and each organ was calculated by the ratio of area under the concentration-time curve after oral administration (AUCpo) to AUCiv. Each organ appeared to have their own bioavailability (i.e., liver 39%, kidney 97%, heart 37%, lung 18%, spleen 10%, and brain 72%), where plasma was 46%. These results highly suggested that different Se distribution in organs by the different route of administration was due to the different metabolic profile.

Decreased blood cell counts were not observed in cattle living in the “difficult-to-return zone” of the Fukushima nuclear accident

Abstract White blood cells, especially lymphocytes, are susceptible to radiation exposure. In the present study, red blood cell, total white blood cell, and lymphocyte counts were repeatedly measured in cattle living on three farms located in the “difficult‐to‐return zone” of the Fukushima nuclear accident, and compared with two control groups from unaffected areas. Blood cell counts differed significantly between the two control groups, although almost all the values fell within the normal range. The blood cell counts of the cattle in the “difficult‐to‐return zone” varied across sampling times even on the same farms, being sometimes higher or lower than either of the two control groups. However, neither a statistically significant decrease in blood cell counts nor an increase in the rate of cattle with extremely low blood cell counts was observed overall. The estimated cumulative exposure dose for the cattle on the most contaminated farm was within a range of 500–1000 mSv, exceeding the threshold for the lymphopenia. Because of the low dose rate on these farms, potential radiation damages would have been repaired and have not accumulated enough to cause deterministic effects.

Whole-Body Counter Evaluation of Internal Radioactive Cesium in Dogs and Cats Exposed to the Fukushima Nuclear Disaster.

As a result of the 2011 nuclear incident that occurred at the Fukushima Nuclear Power Plant, a large number of abandoned dogs and cats were left within the disaster zone. A small number of these animals were rescued and cared for at shelters. Prior to the dispersal of these animals to their owners or fosterers, we evaluated the degree of internal radiocesium contamination using a specially designed whole-body counter. We conducted 863 non-invasive measurements of gamma rays due to internal radioactive cesium for 68 dogs and 120 cats at one shelter. After plotting graphs of 137Cs density we generated exponential functions of decay from seven dogs and six cats. From the regression formulae, we were able to determine the biological half-lives as 38.2 days for dogs and 30.8 days for cats. We found that in dogs there was a correlation between the biological half-life of radioactive cesium and age. Using our data, we estimated whole-body densities for each cat and dog at the time when they were rescued. We found that there were deviations in the data distributions among the different species, likely due to the timing of rescue, or living habits prior to rescue. A significant correlation was found when extracted feline reproductive organs were analyzed; the coefficients for the estimation of whole-body densities were approximately 7-fold higher than those based on the extracted feline reproductive organs. This may be due to the fact that majority of the radioactive cesium accumulates within muscular tissue with less distribution in other organs. It is possible to plan the appropriate management period in an animal shelter based on the use of the biological half-life of radioactive cesium calculated in this study. We believe that the correlations we uncovered in this work would be of great use for the management of companion animals in the event of a future nuclear accident.

Development of Dual‐Energy X‐ray CT using Synchrotron Radiation

Monochromatic x‐ray CT at two different energies provides information about electron density without ambiguity due to the beam hardening effect. This information makes the treatment planning for heavy‐ion radiotherapy more precise. We have started a feasibility study on the dual‐energy x‐ray CT by using synchrotron radiation. We developed a linear scanning CT system in order to evaluate what precision in the measurement was achieved. The experiments were carried out using monochromatic x‐rays of 40, 70 and 80 keV. Comparison of measured electron densities with the theoretical values proved that these values were in agreement in 0.9 % on average. We have developed a 2D‐CT system with a two‐dimensional scintillator array to take images in a short time. At present, it has been proved that the electron density is measured in the precision of about 1 % with the 2D‐CT system. Effective atomic numbers are obtained as well from the dual‐energy x‐ray CT. The CT images are reconstructed based on each of the electro...

Influence of Gestation and Lactation on the Levels of Plasma Folates in Sows

Since the folate level decreases in plasma before its depletion, and this decrease in plasma is paralleled by a reduction in red blood cell folate, the levels in plasma are important clinical indicators that reflect folate status of the body of many mammalian species.1,2 Pregnancy is one of the important factor that is associated with negative folate balance, including progressively reduced serum and erythrocyte folate levels, and increased urinary folate excretion.1 N5-methyltetrahydrofolic acid (CH3-H4PteGlu) generally comprises most or all of the plasma folate in many mammalian species. Recently, however, tetrahydrofolic acid (H4PteGlu) was found to exist as the primary form of folate in the plasma of pigs,3 suggesting interspecies differences in folate metabolism.

Contribution of plasma protein binding to the stability of tetrahydrofolate in pig plasma.

Plasma folate takes important roles in folate homeostasis in the body1. The principal folate in plasma has been recognized to be is 5-methyltetrahydrofolate in many species2.