Neutrons for BNCT using the near threshold ⁷Li(p,n)7 ⁷Be reaction have typical energies ranging from a few KeVs to about a 100KeV.
An effective thermal neutron distribution in the living body can be achieved by introducing BDE (Boron dose enhancer) in the irradiation field (i.e., at the surface of the body).
It was previously shown that the dose distribution in the living body can be modified according to the requirements of the treatment condition by varying the BDE thickness and/or material type.
In this study, we verified the effect of changing the BDE diameter on the dose distribution both along the central axis and off-axis directions for a 4.63cm beryllium BDE.
Simulation calculations for the neutron and gamma ray production in the lithium target were carried out by means of Lee's method. While particle transport was performed using the MCNP4C2 code.
The treatable protocol depth (TPD) which is the central axis depth that satisfies the prescribed tumor dose and the tolerance dose from heavy charged particles (PD(hcp)) and the tolerance dose from gamma rays (PD(γ)) for normal tissue was used to evaluate the dose distributions in a water phantom obtained for each BDE diameter.

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It is known that high LET Heavy ion beams generally causes more serious damage than X rays. However, the difference between heavy ion beams and X rays in repair response is still unclear. The purpose of this research is to elucidate the difference in DNA damage and repair response by observing three proteins, gamma H2AX, phosphorylated DNA-PKcs and phosphorylated ATM. These proteins were stained by the immunostaining method, were observed for the foci and were quantified by counting the number of foci. Initially, gamma H2AX foci, which are known to be the indication of DSB, were observed to investigate the DSB induced by heavy ion beams. In C ion (LET=70keV/um) and Fe ion (LET=200keV/um) irradiated cells, there were larger and brighter foci than in the X-irradiated cells. This is because the DSB induced by C ions or Fe ions were more localized than the DSB induced by X rays. Secondly, to investigate the cell reaction to DNA damage induced by heavy ions, phosphorylated DNA-PKcs at threonine 2609 (T2609) and phosphorylated ATM at serine 1981 (S1981) foci were observed. After C ion and Fe ion irradiation, the peak for the number of T2609 foci was significantly delayed in normal human fibroblast compared with X-irradiated cells. When the time variation of the number of S1981 foci were observed, the delay of the peak was more distinct in the Fe ion case than in the C ion case, because Fe ion beams may have higher LET than C ion beams. This result may indicate that the difference in LET may change the repair response to irradiation.

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We studied the localization of phosphorylated H2AX in cultured human fibroblasts after irradiation with heavy ion beams. Asynchronous human normal fibroblasts (NB1RGB) were irradiated with X-rays, carbon ion beam (LET is about 88 keV/µm), Si ion beam (220 keV/µm) and Fe ion beam (440 keV/µm) at room temperature. Phosphorylation of H2AX in irradiated cells was measured from 0 to 24 h after irradiation monitored by using flow cytometry. Phosphorylated H2AX increased just after irradiation of each radiation and reached maximum around 30 min. Phosphorylated H2AX was then decreased quickly for cells irradiated with X-rays but presented longer for Fe beams. Foci of γ-H2AX on cell nucli were counted under the laser scanning confocal microscopy. Focus was not visible just after X-irradiation, but obvious after Fe ion irradiation. Number of foci per nucleus was increased with increasing dose of each radiation at 30 min after irradiation.

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We reported that carbon-ion beams induce efficient cellular sensitivity and apoptosis as compared with X-rays in a p53-independent manner. Here, we have studied the radiation sensitivity and apoptosis of a human cultured gingival cancer cell line (Ca9-22) having mutated p53gene after exposure to Fe-ion beams or X-rays. Fe-ion beams were accelerated to 500 MeV/u by a heavy-ion medical accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS). For X-ray irradiation, a 200 kVp X-ray generator (PANTAK-320S, Shimadzu) was used. The cellular sensitivity was determined by colony-forming assay. The induction of apoptosis was measured by Hoechst 33342 staining of apoptotic bodies.
As a result, 10% survival dose (D₁₀) was about 2 Gy and 7 Gy to Fe-beams and X-rays, respectively. The relative biological effectiveness (RBE) of the Fe-ion beam to X-ray was 3.5, calculated at D₁₀. Little difference was found in kinetic patterns (time course) of apoptosis induction at D₁₀ dose. The percentage of apoptosis after irradiation at D₁₀ with Fe-beams was 1.2 times higher than X-rays. Furthermore, the induced frequency of apoptosis with Fe-beams was 4 times higher than X-rays after 2Gy irradiation.
These findings suggest that heavy-ion beams induced more efficiently cell lethal and apoptosis than X-rays, and are useful even to p53-mutated patients in cancer therapy.

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It was reported that the dose-rate effects of X-rays or gamma-rays are, it is reported that the biological effectiveness decrease with decrease of the dose-rate (Joel S et al, 1973). Radiosensitivity of cell survival changes with the dose-rate among 0.2 Gy/hr - 60 Gy/hr (HP Leenhouts et al, 1990), for example. There are no reports concerning the change in radiosensitivity by heavy-ion exposure with different dose-rate. The dose-rate of heavy-ion is adjusted arbitrarily in the experiments in HIMAC. However, the influence of the dose-rate is not take account in the results. Thus, we studied the dose-rate effect on radiosensitivity of carbon-ion beams on cell survival.
Exponentially growing HSG cell line was irradiated and this was established from a human salivary gland tumor cultured in Eagle's MEM medium supplemented with 10% FBS and antibiotics. A 290 MeV/u carbon-ion beams accelerated at HIMAC having 18cm irradiation field and 70keV/μm were used with the dose-rate at 0.5, 6.0, 30, 36, 150, and 600 Gy/hr.
Dose-rate effect was not observed within the dose-rates tested and all the survival data were plotted on a survival curve. It is also found that there are no significant changes in survival parameters by the dose-rate. As in conclusion, there are no dose-rate effects on cell survival by carbon beam irradiation. Alternation of the dose-rate in experiments will not affect on experimental results. We will report some results from reference ⁶⁰Co gamma-rays experiments.

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The reversed dose rate effects of mutation induction are often reported for fission neutron radiation. Our former investigation revealed that the reversed dose rate effects might be caused by hypersensitivity of G2/M cells for mutation induction by high LET radiation. To clarify whether this phenomenon could occur in any high LET radiations, a novel hyper-sensitive mutation detection system has been developed. The system uses hamster fibroblast cells carrying a normal human X-chromosome, and we found that the mutation frequencies obtained from our system is 100-fold higher than that from conventional system using an internal Hprt gene. This suggests that the system appears to be able to detect a wide spectrum of mutations, even mutations that affect expression of any important genes in neighbor of the Hprt. Using the system, we analyzed low dose-rate effects of heavy particle beam (carbon 290 MeV/u beam) with different LETs, Because a lower limit of radiation dose for mutation induction with the system was found to be around 0.1 Gy, this enabled us to perform cell irradiation at lower dose rate about 0.84 mGy/min. Apparent reversed-dose rate effect was observed for higher LET (66 keV/µm) but not for lower LET (13 keV/µm). The results suggest that the reversed dose-rate effects occur dependent on radiation LETs.

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Genomic instability, mutation, cell death, carcinogenesis, and DNA double strand breaks have been considered as a result of radiation exposure. However these responses were observed in unirradiated cells located near by irradiated cells or co-cultured in the same medium. Although the mechanisms of these cellular responses are not clearly understood, these responses were reported as a radiation induced bystander effects. Recent studies indicate that bystander effects are transmitted by gap-junction intercellular communication or by releasing of soluble factors into culture medium.
Human normal fibroblast cells, GM05389, were irradiated with 20Ne7+ (LET = 430 keV/μm) ion beam, by using heavy ion accelerator at TIARA of JAERI-Takasaki. After irradiation, cells (donor cells) were cultured in fresh medium for 24 hours, and then the medium was transferred into other unirradiated cells (recipient cells). After further incubation, chromosomes of recipient cells were observed by using premature chromosome condensation method.
From these analyses, the induction of chromosomal aberrations was clearly observed in recipient cells that were not irradiated directly. In this study, by the addition of drug to prevent the action of DNA-PKcs, an well known enzyme which takes part in repair of DNA double strand break, into donor and recipient cells, the effect of DNA-PK in the bystander effect was also observed.

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It has been widely accepted that high-LET radiations effectively kill cells, thereby having been clinically applied to cancer radiotherapy. Normal cells, however, coexist not in cancerous tissue but also in the periphery of the targeting region of radiation treatment. We here therefore investigated the cell-killing effect of six kinds of high-LET radiations in confluent, density-inhibited, normal human diploid fibroblasts. Ion-beam irradiation was performed at TIARA in JAERI-Takasaki. RBE values, relative to the dose of γ-rays (0.2 keV/μm) giving 10 % survival, for ⁴He²⁺ (16 keV/μm), ¹²C⁶⁺ (76 keV/μm), ¹²C⁵⁺ (108 keV/μm), ²⁰Ne⁸⁺ (321 keV/μm), ²⁰Ne⁷⁺ (437 keV/μm), ⁴⁰Ar¹³⁺ (1610 keV/μm), were 1.4, 3.0, 3.9, 3.4, 2.7, 0.8, respectively. Results of the experiments to evaluate the late-arising effect in the progeny of cells surviving heavy ions, and bystander effect, will also be shown.

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Heavy ion particles are utilized for cancer therapy, because they show the higher LET and the typical Bragg peak, both lead to kill targeted cancer cells efficiently. However, we have known little about intracellular DNA damage induced by heavy ion particles. In this study, we estimated the number of DNA damage including strand breaks and/or oxidative base lesions, and evaluated their localization using pDEL19 and lambda DNA as target substrates. These DNA were irradiated by g-rays (0.2 keV/µm), carbon (13 keV/µm) and iron ions (200 keV/µm), and analyzed by gel electrophoreses and aldehyde reactive probe method. The result showed that total damage per dose were decreased with increase in LET. Even clustered damage per dose also were decreased with increase in LET. It suggests that quality of clustered damage is more important to elicit the biological effect than quantity of that. Quality of clustered damage contains the number, the species and the disposition of respective lesions in each clustered damage. Therefore, we also report here our examined procedures to evaluate the quality of clustered damage.

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Heat shock protein90 (Hsp90) is a molecular chaperone that plays an important role in the stability of unstable proteins. Hsp90 is involved with maintaining the conformation and function of key client proteins involved in cell proliferation and cell cycle progression. Tumor Hsp90 is present entirely in multi-chaperone complexes. Thus, it can become an effective means in cancer therapeutics to disrupt chaperone functions of Hsp90.17-Allylamino-17-demethoxygeldanamycin (17-AAG) which inhibits Hsp90 has effect on apoptotic processes such as the phosphatidyleinositide 3-kinase-Akt kinase cascade. The combination of radiation and 17-AAG extremely increases cell killing. There is a possibility that the enhancement of radiation induced cell killing by 17AAG would not only relate to apoptosis but DSB repair inhibition. So we investigated whether 17-AAG affects DSB repair using two human carcinoma cell lines. These cell lines were then incubated in medium containing 17-AAG 24hr before X-ray exposure in all experiments. Constant field gel electrophoresis clearly indicated that rejoining of DSBs was impaired when exposed to both X-ray and 17-AAG. Furthermore, we are investigating which DSB repair process namely, NHEJ or HR, is principally affected.

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Stable nitroxide radicals such as TEMPO and carbamoyl-PROXY (CM-PROXYL) are reportedly good radiation protectors and we demonstrated in the previous meeting that methoxycarbonyl-PROXYL (MC-PROXYL) is also a good radiation protector. In the present study, we prepared another 4-substituted PROXYL, hydroxymethyl-PROXYL (HM-PROXYL) and compared these three PROXYLs with respect to radiation protection, prevention of DNA damage, and distribution in mice.
The PROXYLs had different in vivo radiation protection activity assessed as a 30 day-survival of mice (C3H, male) after X-ray irradiation.; HM-PROXYL > MC-PROXYL ≈ CM-PROXYL. On the other hand, their protection in cellular level examined as the recovery of colony formation inhibited by X-ray irradiation was similar among them: HM-PROXYL ≈ MC-PROXYL ≈ CM-PROXYL. Further, in vitro radiation protection against DNA damage measured by cleavage of plasmid DNA (pBR322) or formation of 8-OHdG in salmon DNA caused by X-ray irradiation was also similar among them. Oxidation potential of CM-, MC-, and HM-PROXYL are 0.662, 0.677 and 0.589 V, respectively, and reduction potential of them are -0.688, -0.687 and -0.686 V, respectively, showing only little difference. The concentration in the blood and bone marrow showed the order of HM-PROXYL > MC-PROXYL ≈ CM-PROXYL. Therefore, the difference of in vivo radioprotection of these PROXYLs could be mainly explained by the difference in the distribution of these compounds in the body.

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Purpose : Tetrahydrobiopterin (BH₄) is a cofactor of nitric oxide synthase (NOS) and has an antioxidant activity. In our previous study, it is found that various antioxidants and NO reduce γ-ray-induced chromosome aberrations. The effect of BH₄ on γ-ray-induced micronucleus (MN) frequency of RAW264.7 cells was investigated in this study.
Methods : Mouse macrophage-like RAW264.7 cells were irradiated with 5Gy γ-ray in the presence or absence of sepiapterin (SP), a precursor of BH₄ biosynthesis. To determine MN frequency, cells were fixed to a microscope slide and stained with Giemsa and the number of MN per 500 binucleated cells was scored under a light microscope. Intracellular BH₄ concentration was measured by using reversed-phase high performance liquid chromatography (HPLC).
Results and Discussion : Treatment of RAW264.7 cells with 1μM SP, a precursor of BH₄, reduced the 5Gy γ-ray-induced MN frequency by 65% at 18 and 24h post-treatment. This effect was blocked by N-acetyl-5-hydroxytryptamine and methotrexate, inhibitors of BH₄ biosynthesis. Intracellular BH₄ concentrations were peaked at 6h and kept on a high level until 24h after SP treatment. These results suggest that the reduction of γ-ray induced MN frequency by SP would be not necessary due to an antioxidant activity of BH₄ and also other protective mechanisms would be included.

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Purpose:The following was confirmed when we reviewed antitumor effect, blood cell augmentation, an antioxidation effect and subset analysis in T-cell, NK cell activity, TNF -Α, INF-Γ, IL-2, interleukin-12 we paid our attention to macro-glucan, Agaricus, AHCC, antitumor action to have, antioxidation of placebo, adjuvanticity, and to review that mechanism of antitumor effect in organism was immunological enhancement.Methods:Because increase of helper T cell, cytotoxic T cell and suppressor T cell was observed in leukocytes, lymphocytes, increase of a monocytes, and subset of T lymphocyte by Agaricus and macro-glucan administration, by Agaricus, AHCC and macro-glucan administration, immunocompetence activity was found.Results:Immunocompetence activity was found in AHCC from augmentation of NK-cell and cytotoxic T cell and increase of suppressor T cell having been observed.Because Agaricus, AHCC and macro-glucan administration, found antioxidation ability and radical scavenging effect we can expect a radiation protection effect.Conclusion: Tumor growth depression was suggested by Agaricus, AHCC and macro-glucan administration, and, as for the mechanism, it was suggested activity of a macrophage by immunological enhancement and TNF -Α, INF-Γ, IL-2, increase and NK cell of interleukin-12 when active.Immune therapy will attract attention in cancer therapy more and more in future.Therefore, we were able to contribute as fundamental researches of the immune therapy that was specific for carcinoma in cancer therapy.

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EF2001 was made from Enterococcus Faecalis, and it has radiation protection effects by protection of the intestinal mucosa in the absorption function of the carcinogenesis materials. We used animals were C3H mice bearing SCC-7 tumor. The mice irradiated with X-ray hole body after intraperitoneal infection of EF2001. Body weight was smaller in mice injection EF2001, as control group after 3 days. No apparent difference was found between two groups injected EF2001.There was tendency to prolong the survival in the groups injected EF2001. In the intestine, mucosal damage was protected in both EF2001 12 mg and EF2001 24 mg groups.The tendency that damage was few included a one of EF2001 24 mg group in the small intestine. Activities of NK cells were enhanced 1.46 and 1.94 times in EF2001 24 mg groups respectively.EF2001 doesn't absorption of nutrient matter, and there is function that absorption does Trp P-1 and Trp P-2 which is carcinogenesis. The results of this study confirmed, EF2001 has effect of radiation protection. EF2001 can absorption of carcinogenesis materials selectively.

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We previously reported that glycine betaine reduced the chromosome aberrations caused by either γ-rays or carbon ions. In this study, we investigated the effects of glycine betaine on bone marrow death and intestinal damage by γ-rays or carbon ions. C3H/He female mice, aged 14 weeks, received an i.p. injection of glycine betaine at 15 min before whole-body irradiation with γ-rays or 50 keV/µm carbon ions. The irradiated mice were observed to determine the mortality for 30 days after exposure. Also, the mice were killed at 3.5 days after the exposure to determine the intestinal damage. The jejunum was fixed in formalin and then stained with H&E. The number of crypts per transverse circumference were counted using a microscope. For the bone marrow death, glycine betaine significantly (p < 0.05) increased the percent survival for both radiations. For the intestinal damage, glycine betaine significantly (p < 0.05) increased the crypt survival for γ- rays, but not for carbon ions.

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Immune function degradation is noted it for a side effect of radiotherapy. In this study, we reviewed the presence about anticancer activity by lignin of an active ingredient origin of a pinecone, antioxidation, adjuvanticity. As for the leukocytes, the lymphocytes change, 2Gy irradiated lignin after administration in 360mg/kg abdominal cavity per ICR mice body weight for three weeks. Even antioxidation activity measured SOD activity in serum equally. About immune globulin total IgG, the measurement of quantity of IgM, we used C3H laboratory mouse and measured total IgG and quantity of IgM. About analysis of T lymphocyte subset, fluorescence staining of flow cytometry assumed lymphocyte of C57BL mouse it and analyzed CD4 and CD8. About a radioprotective effect of lignin for a blood cell, there were leukocyte count and lymphocyte counts decrease depression effect. In addition, decrease of quantity was accepted about an antioxidation effect and IgG, IgM antibody formation. In addition, there were CD4 by lignin administration and increase of a CD8 positive rate. It was the radical scavenging effect that resulted from radiation exposure and controlled decrease of leukocytes, and lignin prevented degradation of immunology force and controlled immunology force degradation with radiation exposure by increase effect such as activity and T cell activity of a macrophage or INF-Γ, and what radiation protection did was found.

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We examined the effects of glycine betaine on bone marrow death induced by gamma–rays. The 30-day survival rates for glycine betaine-preinjected and -postinjeccted mice were 75% and 55%, respectively, whereas the 30-days survival rate for saline-injected mice was 10%. The number of leukocyte was at a minimum 3 days after irradiation, but the recovery was more rapid for glycine betaine-injected mice than for saline-injected mice. The survival of endogenous CFU-S in glycine betaine- and saline-injected mice after irradiation with gamma–rays was examined. The number of endogenous CFU-S in glycine betaine-injected mice was higher than that in saline-injected mice. Hydroxyl radical-scavenging activity of glycine betaine was increased by glycine betaine in a dose-dependent manner. The protective effect of glycine betaine on bone marrow death would be due to higher survival or recovery of stem cells.

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Ionizing radiation generates reactive oxygen species (ROS), such as superoxide, hydroxyl radicals and hydrogen peroxide, which participate in DNA damage and lipid peroxidation. Manganese (III) -5,10,15,20-tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) is well known as cell-permeable superoxide dismutase (SOD) mimetics. In this study, we investigated the protective effects of MnTMPyP on the mortality after irradiation. Eight-week-old female ICR mice were given whole-body irradiation with ¹³⁷Cs γ-rays at a dose of 8.2 Gy (0.93 Gy/min). Mortality of the irradiated mice was determined for 30 days after exposure. When the mice were given a single i.p. injection of MnTMPyP at a dose of 6, 60 mg/kg, or saline before irradiation, the survival rates were about 40%, 50% and 10%, respectively. The survival rate of group continuously treated with 6 mg/kg MnTMPyP for 2 weeks was about 50%. These results support that MnTMPyP might be a potential radioprotector. The conceivable mechanism of the radioprotective effect of MnTMPyP would be the scavenging of the free radicals because MnTMPyP has ROS scavenging activity. Effect of MnTMPyP after irradiation on the mortality is now underway.

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Lactoferrin is an iron-binding glycoprotein with a molecular weight of about 80,000. It The radioprotective effect of lactoferrin was studied in mice following whole-body X-ray irradiation. C3H/He mice were used in this experiment. The mice were separated tow groups One group(50 mice) were fed an AIN-93 diet, which contained 0.0007 % w/w lactoferrin. The other group (50 mice) was fed an AIN-93 diet and water ad libitum. He mice were kept for 30 days on each diet, and were then exposed 6.8 Gy of whole-body irradiation. The survival rates of these mice were observed within 30 days after irradiation. The survival rate of lactoferrin-diet mice were about 23% higher than those of mice on a standard diet, and the rates dropped sharply to a plateau at day 10 after X-ray irradiation. The scavenging abilities of lactoferrin were evaluated by the ESR spin-trapping method. Lactoferrin is a radical scavenger of hydroxyl radicals and the observations suggested that radical trapping or scavenging might cause the biological response.

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Exploration and development of new therapeutic radioprotectors is of great concern for both public health and academic research. Combined application of radioprotectors is as a strategy aiming at reduction of toxicity and increase of radioprotective efficacy. We reported previously that Na₃VO₄(VD) had potential biofunctions including suppression of radiation-induced apoptosis and reduction of radiation-induced detrimental effects on fetal mice from a moderate to a high dose(1 ~ 3.5 Gy). These results suggested an abundance of pharmaceutical candidates for possible radioprotectors from inorganic chemicals and pointed to the further investigation on the radioprotective effect by combination of several anti-apoptosis agents against a relatively low dose(0.5 Gy). In the present study, pregnant ICR mice were irradiated with X-rays on E12. Either VD or its combination with a p53 inhibitor(pifithrin) and a pan-caspase inhibitor(Z-VAD) was intraperitoneally administrated at 30 minutes after irradiation. The dams were left for delivery and the neonates were monitored for postnatal development. Administration of VD alone significantly reduced the inhibitory effect on postnatal development, and combined application showed a more statistically remarkable efficacy. These findings indicate that VD could reduce the detrimental effect of prenatal irradiation on postnatal development in mice. Administration of combined anti-apoptosis agents would have a great possibility for clinical application in the future as a therapeutic treatment for low dose radiation exposure.

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S-1 is a novel 5-fuorouracil derivative chemotherapeutic agent composed of tegafur (a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine that inhibits degradation of 5-FU, and oxonate that regulates the phosphorelation of 5-FU in the gastrointestinal tract to redue the adverse effects. Oxaliplatin (trans-1-diaminocyclohexane-oxalatoplatinum; L-OHP), a third-generation platinum compound, has shown promising antitumor activity in the many types of cancer. The purpose of the present study is to investigate whether combined S-1 and Oxaliplatin and radiation are effective in the treatment of 5-FU resitant tumors. The study was performed using a human colon cancer cell line, designated DLD-1/FU, which is resistant to 5-FU. The cells were implanted into the leg of nude mice. When tumor volume reached 80-100mm3, treatments were begun: treated with a vehicle (control), treated with a single dose of 5Gy local tumor irradiation, 8mg/kg of S-1 or 5mg/kg of Oxaliplatin, and combination treatments. Tumor growth was measured every 2 to 3 days, and the effects of the treatments were expressed by tumor growth delay. The results showed that the combined treatment with S-1 and Oxaliplatin plus tumor irradiation 5Gy was effective in delaying tumor growth compared to the drug only, or drug plus irradiation. Current experiments explore cellular and molecular mechanisms underlying the interaction between S-1, Oxaliplatin and radiation.

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Our previous study has demonstrated that 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd) enhanced radiation-induced inhibition of tumor growth through the apoptosis induction and the reduction of cell proliferation in colon26 solid tumor. In this study, we focused on hypoxic cell and examined the effects of ECyd on tumor cells in hypoxic condition both in vitro and in vivo.
Human gastric adenocarcinoma MKN45 cells in a gas-exchangeable chamber were exposed to hypoxic condition (oxygen concentration = 3 mmHg) by passing 100% N₂ gas continuously. An increase in the accumulation of HIF-1α was observed when cells were incubated under hypoxia. However, HIF-1α expression was decreased to the level of normoxic condition when cells were incubated under hypoxia in the presence of 5 μM ECyd. In MKN45 xenograft, a significant reduction in tumor growth was observed in mice treated with a low dose of X-rays and ECyd compared with X-rays or ECyd alone. These results suggested that ECyd enhanced radiation-induced inhibition of tumor growth through the inhibition of hypoxia-induced expression of survival factors. The detailed mechanism of tumor suppression will be discussed.

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The effects of amrubicin (AMR) and its active metabolite, amrubicinol (AMROH), on the sensitivity of human lung adenocarcinoma A549 cell line to hyperthermia at 44°C were investigated, and the cell phase response and the kinetics of apoptosis / necrosis were analyzed. Sequential treatments with AMR (2.5 µg/ml) or AMROH (0.02 µg/ml) prior to 44°C hyperthermia resulted in additive thermo-enhancement effect by reducing not only survival but was shoulder wide. The thermo-enhancement effects of DNA topoisomerase II inhibitor, AMR, AMROH, adriamycin (ADM) and etoposide (VP-16) on 44°C hyperthermia were compared, and these agents exhibited comparable thermo-enhancement effects. The cell phase response with each agent were studied. It is reported that ADM is sensitive to S phase and VP-16 is sensitive to G₂-S phase. In our study using synchronized A549 cells, AMR or AMROH did not elicit cell phase responses irrespective of the concentration. The incidence of apoptosis was observed at 48 and 72 h after AMROH for 4 h, 44°C hyperthermia for 35 min alone or the combined treatment, which apoptosis was not significantly induced after any treatment. Furthermore, the incidence of necrosis was examined as well as apoptosis. The necrosis induced after the combined treatment was circa 3 times higher than that in either of the single treatments.

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Tempo, a nitroxide, exerts an SOD-like antioxidant activity against ROS. Reportedly, Tempo inhibits ROS-induced apoptosis in thymocytes, and activates JNK1 to induce apoptosis in breast cancer cells. In this present study, we observed sensitization of heat-induced apoptosis by 5 mM Tempo in the pheochromocytoma cell line (PC12). We investigated the sensitization mechanisms. 5 mM Tempo or 44C/10 min heating was non-apoptotic to PC12 cells. However, the combined treatment markedly sensitized PC12 cells to apoptosis, as induced by 44C/30 min. Although levels of Bcl-2, Bcl-XL and Bax in lysates were not altered, Bax was rapidly translocated to mitochondria after the combined treatment and 44C/30 min, followed by cytochrome c release. The combined treatment and 44C/30 min activated JNK 1, which was partially inhibited by the inhibitors of JNK. Our results suggest that sensitization of Tempo/heat-induced apoptosis may involve Bax-mediated increase in outer mitochondrial membrane permeability resulting in cytochrome c release.

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The purpose of this study is to evaluate ¹⁴C-thymidine as a tracer, to detect radiation damages in gut.
In unirradiated mice, ¹⁴C-thymidine accumulated in gut within 30 min after an intravenous injection and reached a plateau. The plateaued accumulation of ¹⁴C-thymidine in gut was 18-folds higher than that in plasma.
We examined the thymidine accumulation in irradiated gut. Mice were given whole body irradiation with carbon-ion (290MeV/u, 6cm-SOBP, 20keV/µm). Accumulation in gut of 2-[¹⁴C]-thymidine decreased with an increase of carbon-ion doses (1-9 Gy), whereas that of 6-[³H]-thymidine was independent of radiation dose. These results suggest that the difference of isotope-labeled position causes change of thymidine kinetics. In addition, we investigated blood flow in gut using ¹⁴C-IMP. The blood flow decreased by 25 % after 1 Gy irradiation or over, suggesting that blood flow should be taken account for the evaluation by ¹⁴C-thymidine.
Furthermore, to evaluate the radioprotection, mice were pretreated with bFGF and MK801. Radioprotectors of bFGF and MK801 increased DNA synthesis in gut by a factor of 1.5 at 84 hours after carbon-ion (9 Gy) irradiation while number of crypts was not affected by radioprotectors. These findings demonstrated that the thymidine uptake in vivo could be an appropriate marker for investigating gut responses and radioprotection.

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To enhance the efficacy of local irradiation of malgnancies, it is important to induce inflammation and to recruit tumor specific T cells and dendritic cells (DC) at cancer sites. Macrophage inflammatory protein 1 alpha(MIP-1 alpha,CCL3)is a chemoattractant for DCs, monocytes and lymphocytes, and have a crucial role in development of inflammation and immune response. We studied the effect of MIP-1 alpha derivative, eMIP (formerly called BB10010) on irradiated subcutaneous tumor in mice. Mice were subcutaneously implanted with Lewis lung carcinoma cells in the right flank. When the diameter of solid tumor reached approximately 1cm, local tumor irradiation with 6 Gy was applied. After 24 h, the mice were received eMIP intravenously. Since then, eMIP was administrated once a week. The effect of irradiation and eMIP was evaluated by measuring the tumor volume.Radiation with 6Gy reduced the tumor volume by 50%, and administration of eMIP enhanced the efficacy of radiation by further 30 % (total reduction rate:80%). The optimal dose of eMIP was 2~5 microgram/mouse in combination with radiation at 6Gy, and eMIP did not have anti-tumor activity by itself in this system. The tumor treated with both radiation and eMIP showed marked infiltration of CD4 and F4/80 positive cells and a slight increase of CD8 positive cells compared with control and radiation-treated group. The results indicate that eMIP enhances the radiation induced inflammatory response and/or tumor specific immune reaction in tumor, and this might be a new approach in the radiation therapy.

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[Purpose] We have studied the effects of A-bomb radiation on human germ cells, that is, whether the mutation rate has increased significantly in the offspring of A-bomb survivors compared with controls at DNA level. To conduct this study at genome-wide, we have been introducing a microarray based comparative genomic hybridization (array CGH) method. Before starting a large-scale study, we conducted a pilot study to examine the feasibility of this method.
[Experiments] We constructed an array with about 2400 Bac-clones. These clones are distributed about every 1.2 Mb across human autosomes. The results of preliminary studies demonstrated that our CGH system could reliably detected one copy change from normal duploidy. So, we have done a pilot study, in which we used genomic DNA from 40 offspring of A-bomb survivors and 40 members of a control group.
[Results and discussion] Variants observed once in this population, termed "rare variants", were identified on 14 Bac-DNA targets. The results from family studies revealed that these rare variants were inherited from at least one parent. Thus, until now, no de novo mutant was identified. We characterized these rare variants by Southern blot analysis using pulse field gel electrophoreses, FISH method, quantitative PCR, and sequencing. These results demonstrated that our array CGH system can reliably detect the variants larger than 50 kb. From our data, we consider that array CGH is one of the most useful techniques for our research purposes. Now, we are planning a larger population study.

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Purpose: To report two independent ophthalmologic studies recently conducted in A-bomb survivors. Subjects and Methods: Subjects are (1) 873 persons who underwent slit lamp examinations during 2000 – 2002 and (2) 3761 persons who underwent health examinations during the same period. Dose response relationships between A-bomb radiation and levels of lens opacity by the Lens Opacity Classification System in study (1) and between the A-bomb radiation and a prevalence of postoperative cataract cases in study (2) were analyzed. Results: In logistic regression analyses after adjusting for city, age, and sex, odds ratios at 1 Sv were 1.30 (95% CI, 1.10-1.53) in cortical cataract and 1.44 (95% CI, 1.19-1.73) in posterior subcapsular cataract in study (1) and 1.41 (95% CI, 1.26-1.58) in postoperative cataract cases in study (2), respectively. Conclusion: Independent cataract indicators consistently showed significant dose responses with A-bomb radiation, suggesting a presence of late onset radiation-induced cataract.

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Results from atomic bomb survivor studies of ovarian cancer mortality and incidence in the LSS cohort, conducted at the RERF, demonstrated a dose response. The present study is on intensive pathology review of possible benign and malignant ovarian tumors. Purpose of the present report is to estimate histological-type-specific radiation risk of ovarian cancer as well as benign tumors for the period of 1950-88.Association with radiation was suggested for common epitherial carcinoma, which account for 90% of all histological types of malignant ovarian tumors. The major types of common epithelial carcinoma are serous and mucinous carcinoma. The mucinous type seems to be less radiogenic than serous type. Background ovarian cancer mortality and incidence rates are increasing in Japan. In the current study the increasing trend of background rate seems to be less steep for serous type, which is more strongly associated with radiation. This may explain, at least in part, the weaker dose response for ovarian cancer as a whole in recent years. The distribution of benign ovarian tumors by histological type is: common epitherial tumors (60%), sex-cord stromal tumors (12%), and germ cell tumors (28%). For all of these tumors, association with radiation was observed, and the relative risk for sex-cord stromal tumors in particular was greater than those of other histological types in the tentative analysis. As for common epithelial tumors, like malignant ovarian tumors, association with radiation was suggested for serous tumors, but not for mucinous tumors.

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We compared cancer mortality between two groups of Nagasaki A-bomb survivors; one group was bombed in areas shielded by mountains located east and east-south at about 2.5 km from the hypocenter, while the other was bombed in unshielded areas in the south at a similar distance from the hypocenter. Cancer mortality from 1 January 1970 to 31 December 2000 in 1541 survivors bombed in the unshielded area was 1.36-fold (95%CI: 0.95-1.93, P=0.09) higher than that in 1627 bombed in the shielded area after adjustment for sex, age at the time of the bombing and attained age. The results suggest that shielding effects by mountain should be taken into account in the evaluation of cancer mortality in Nagasaki A-bomb survivors.

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A total of 1237 Nagasaki A-bomb survivors were interviewed in 1997 and were asked to talk freely about atomic bombing, health concerns, relatives' death, and mental health Their talk was recorded on tape if allowed. The 30-item version of General Health Questionnaire was also administered to assess their mental health conditions. In the present study, we analyzed the talks of 928 Nagasaki A-bomb survivors who completely responded to all items.We used Wordminer for the analysis: we first decomposed texts into words; then evaluated their frequency in the texts; and finally used them for correspondence analysis.We analyzed the significance of the words by sex and age at the time of the bombing. Females bombed under 9 years of age showed the features of child: mother, memory, brother and primary school. Males bombed in their teens showed the features of student: student mobilization and classmate. Females bombed at 20 years of age or over showed the features of woman: husband, children, soldier, marriage and death in action. Males bombed over 20 years of age showed the features of worker: shipyard, factory, soldier and call-up.With respect to the exposure distance from the hypocenter, those exposed at proximal distance showed the features of physical conditions: burns, skin and purpur. Geographical names frequently appeared in those exposed from 2km to 2.9km: Suwa, Tateyama and Mt. Kompira.

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[Purpose] The number of procedures in interventional radiology (IVR) of head and neck has risen owing to their low invasiveness compared with an operation. However, these procedures can deliver a high radiation dose to a patient's skin. Therefore we were aimed at examining the dose distribution, reviewing method for measurement and data processing of dosage in IVR procedures of head and neck.
[Materials and Methods] Thirty-three patients, twelve male and twenty-one female, ranging from 15 to 76 years of age, were included in the study. For measurement of surface dose of patient, a photoluminescence glass dosemeter (PLD) system, Dose Ace (Asahi Techno Glass Co., Japan), was adopted. Forty-seven points were selected for dose monitoring, setting three PLD chips at each point.
[Results and Discussion] As for the exposure dose in patient head, a high tendency was revealed mainly in right temporal and occipital region, and it seemed that this was due to the position of two X ray tubes. Relations with the all exposure time, number of the DSA series, number of DSA frame, dose-area product dosage were examined for maximum dose, but the significant correlation was not found. It was necessary to increase the monitoring point not to miss the highly exposed point, because the dose distribution and maximum dose varied by a case.

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The increasing use of medical radiation, especially in computed tomography (CT) scanning, has raised many concerns over the possible adverse effects of procedures performed without a serious consideration of risks-costs versus benefit in Japan. To understand what concrete situations are considered, particularly in childhood CT-scan, the current diagnostic radiology practice at Nagasaki University Hospital were studied through an examination of the radiology and emergency departments data of a one year period in 2004. The less than one year old children had a significantly higher share in CT examinations compared with other ages. The majority of CT requests were made by the sub-specialist in the tertiary care hospital for particular diagnostic needs so that a cost vs. benefit study appeared to favor the potential provision of valuable information by CT; however many repeated CT requests with negative results were a source of controversy. The management of minor head trauma showed a much higher than recommended level of reliance on CT examination, compared with studies in UK, Canada and USA. The hospital neurosurgery team often takes over the decision making process with considerably higher rates of request for a CT examination. Although the CT indication in University hospital is different from that in other hospitals taking on the secondary emergency care, a lower rate of CT scanning of children is generally desired in accordance with a universal guideline or own policy.

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Tungstate was reported to have a radical scavenging activity. In the present study, the pre administration effect of sodium tungstate on gamma-ray irradiated mouse was examined. Two groups of ICR male mouse were orally administered sodium tungstate solution for seven consecutive days, and the control group received saline, before whole body exposure to gamma radiation (6-12Gy). After irradiation, the measurements of body and tissue weight and hematocrit value and the estimation of DNA damage in tissue and blood cell by the comet assay were conducted. The body weight of tungstate administered mice slightly decreased after irradiation as well as that of control mice, and almost similar degree of spleen weight decrease after irradiation were observed in tungstate administered mice and control ones.

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For monitoring of workers, internal dose due to α, β-nuclides is evaluated by analyses of urine and faces samples. The analysis time of α, β-nuclides is usually longer than γ-nuclides. In a radiological emergency, a rapid bioassay are required. In present study, Sr-extraction resin was used to develop a rapid analysis of Sr-90 in urine samples. Urine samples (200-300 ml) were treated by HNO₃ and Sr fraction was coprecipitated with calcium phosphate. The precipitate was resolved into 8M HNO₃ and loaded onto the Sr-resin (Eichrom Industries Inc). Strontium-90 and/or strontium were eluted by 0.05M HNO₃. Strontium-90 and strontium were determined by a low-background β-counter and an inductively coupled mass spectrometry, respectively. Recovery tests of ⁹⁰Sr spiked between 20-700mBq yielded an good recovery (91-105%). A few ten ng Sr per ml urine was detected by this method. The Sr-resin is expensive, but was economy with time for analyses. It was useful resin in urine analyses.

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The effect of temperature and duration of storage the blood samples on PCC index following high dose exposure Gotoh, Eisuke (egotoh@nih.go.jp)After high dose exposure accident, the absorbed dose should be determined as quick as possible for save the life of victims. The easy and simple protocol of biodosimetry using Giemsa stained prematurely condensed chromosomes has been reported on the previous JRRS meeting. In the present report, we investigated the how the storing temperature/duration of blood samples for chromosome analysis will be affected on PCC index following high dose exposure accident. In the case of the blood was kept at 4oC, the PCC index was drastically decreased, particularly the case of the blood was exposed over 30 Gy. Therefore, the blood sample should be avoided to be store at cool temperature during shipping the blood until start culture of lymphocyte for chromosome analysis.

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Since it was found that tooth enamel is an excellent material for ESR (electron spin resonance) retrospective dosimetry, many studies have used human teeth for estimating doses of radiation accidents. However, human teeth are not always available for retrospective individual dose assessment. In such situations teeth from animals could be used as alternative to human teeth for retrospective dosimetry.The conditions for chemical treatment suitable for extracting enamel from cow teeth were investigated. It is essentially important to remove dentin from tooth enamel for low dose radiation dosimetry in order to avoid interfering ESR signal due to organic radicals. We found that 20% of NaOH and KOH for 5 hours at 40C give the best S/N ratio in ESR spectra.Using this technique, the doses given to cow teeth from the South Ural region, Russia, were investigated, part of which were contaminated by the accidents at the first Russian industrial nuclear facility, Mayak. The doses of most of the teeth were less than the detection limit, but doses up to 200 mGy were obtained from some of the teeth which contain up to 10 Bq/g of 90Sr.

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⁹⁰Sr is one of the most hazardous radionuclides among those released from anthropogenic sources including intentional releases by nuclear plants, radiation accidents and weapon test fallout. ⁹⁰Sr accumulation in teeth can serve as an important information for dosimetry and it has been tested to be estimated by detecting beta rays with the imaging plate (IP). This study aims at evaluation of ⁹⁰Sr distribution in teeth. At present, ⁹⁰Sr deposition is estimated by comparing IP signals between teeth and standard sources containing known amount of ⁹⁰Sr, assuming the uniform distribution. However, obtained teeth have various shapes with varied sizes, while preparation of standard source for each sample is not practical in measuring a number of samples. Moreover, tooth sample is desired to be thin to avoid suppression of the image resolution, but it is difficult to make thin standard source precisely with uniform ⁹⁰Sr distribution. Taking into account above, we have proposed a method which uses numerical conversion of an experimental IP response against ⁹⁰Sr deposition with varied thickness of standard source. The validity of numerical conversion of IP response is verified in this report. For this purpose, the standard sources have been manufactured with varied dimensions and ⁹⁰Sr concentrations. Simulation based on Fermi theory for beta rays production and Monte Carlo method (MCNP-4C) for its transport is examined for the reproducibility of IP signals. The results will be presented.

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Recently, a technique using an imaging plate (IP) is applied for the ⁹⁰Sr concentration determination. However, this IP technique has some difficulties on the determination of absolute values. A difficulty is found in manufacturing the standard source with some kinds of form, though the thickness of the tooth which can be obtained is various. On be half of manufacturing various standard sources, we propose the IP technique combined with self-absorption correction in sample calculated using MCNP Monte Carlo code.At first, the validity of the calculation method was examined through an experiment using standard sources. The standard sources consist of the mixture of paraffin, the powders of extracted tooth dentin from a Techa River area resident and standard bone. They were used for preparation of the pellets melted into aluminum block, with 37.6, 20.9,10.8 Bq/g of 90Sr. Calculated energy deposit in imaging plate (MeV/mm²) was compared with measured signal (PSL/mm²) with respect to their radial distributions, i.e. for various radius of tallies. Experimental and calculated data are in good agreement, which suggests the validity of the calculation method used in the present study. Second, the proposed method is tested on the determination of ⁹⁰Sr concentration in the tooth of the mammal (cow) offered from Mayak, the first nuclear plant in former Soviet Union. As a result, it was found that the accuracy of ⁹⁰Sr determination can be improved by the present method.

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The dose-response relationship of cancer in the atomic bomb survivors is likely to be linear whereas it does not hold true among various stains of mice and rats. The inconsistency causes the gap between epidemiology and biology for considering the dose-response model. Previous approach to dose-response models is based on the amount of damages, such as DSB or chromosome aberration, etc. induced by irradiation. The approach does not consider inhomogeneous characteristics such as genetic variation or individual susceptibility. If we look at individual difference among required doses inducing cancer, a statistical model for tumor doses may be a useful theory in analyzing a dose-response curvature. In the statistical model for tumor doses the cumulative probability of cancer with increasing dose was modeled as a log-normal distribution. We focused on the standard deviation of acute lethality in human and that of tumor doses in various strains of mice and rats reported in the literatures. Our simulation that investigated the effect of standard deviation on the dose-response curvature suggested that the linearity was higher with inhomogeneity of population.

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Radiation protection standards rely heavily on data from the A-bomb Survivors, who were exposed primarily to instantaneous low-LET gamma radiation. Applications, however, are typically to chronic exposure to other radiations, such as indoor radon or high-LET internal emitters (e.g., Plutonium). Information on how to extrapolate risk estimates from one type of exposure to another is lacking. The Japanese Thorotrast and Japanese A-bomb Survivor cohorts provide a means to compare risks in effectively similar populations. Both cohorts have been followed for cause of death over many decades, and both cohorts have relatively reliable dosimetry. Restricting the A-bomb survivor cohort to the same gender and ages at time of exposure (males aged 20 to 40) as the Thorotrast cohort, we estimated subsequent risk of total mortality, solid cancer mortality, and liver cancer mortality. Based on 3,397 deaths in the A-bomb Survivor Cohort (207,314 person years) and 1,548 deaths in the Thorotrast Cohort (83,729 person years), the relative risk of death from all causes (exposed versus non-exposed) was 1.06 for the A-bomb cohort (p = 0.13) and 2.3 for the Thorotrast cohort (p < 0.001). Estimates of excess relative risk (ERR) per Gray for total mortality as well as that for death from solid cancer and death from liver cancer will be reported. Modification of the risk of cancer mortality by age at exposure will also be assessed.

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The aim of the present work has been the development of logical dosimetry for human alimentary tract. In this work, a stomach simple model with stem cells has been developed. Also, specific absorbed fractions for photon and electron to the stomach model have been evaluated in the energy range 10keV-4MeV using Monte Calro simulation. Consequently, it was found that photon SAFs to the stem cell in the stomach are more than those to the stomach wall. Electron SAFs to the stem cell in the stomach were also found to be less than that used in the radiological protection. It is concluded that the Monte Carlo simulation is very useful in the development of logical dosimetry for the stomach and that the determination of target tissue in the stomach is very important for the SAF evaluation.

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Japanese nuclear power plants (NPPs) located in the four main islands of Japan, from Hokkaido to Kyushu and the commissioning years are not same. Results by ecological studies can raise a social concern even for small radiation risk due to NPP routine operation. We analyzed geographical patterns of cancer mortality in all Japan from all lymphoid-hemopoietic tissues (ALHT) and non-digestive organs. Analysis was conducted for specific non-digestive organs and for tumors including benign ones of central nervous system. Those rates in 20 municipalities with an NPP were also examined. The rates in 1972-1997 were examined using Poisson regression taking into account of area, sex, age at death and year. ALHT cancers account for 5.9% of all cancer deaths. Non-digestive cancers account for 35.6% of all solid cancers (non-ALHT). Geographical variation by six area blocks (each block consisted of 7 to 9 prefectures) and five periods was larger in ALHT cancers than in all solid cancers. It was larger in all non-digestive cancers than in all digestive ones. But the variations in both ALHT and all non-digestive cancers were simpler than in leukemia and malignant lymphoma. Specific sites of non-digestive cancers include lung, female breast, uterus, ovary, prostate, bladder, and thyroid. Except ALHT cancers in females, none of geographical pattern of all solid cancers, digestive or non-digestive solid cancers produced any superficial increase in 20 municipalities with an NPP in contrast with the pattern associated with adult T-cell leukemia misclassification for leukemia.

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We measured the amount of AP sites (Apurinic/apyrimidinic sites) in human glioma A172 cells to investigate the effect of extremely low frequency electromagnetic fields (ELF-EMF) at 5 mT. The cells were exposed to ELF-EMF alone, MMS (Methyl methane sulfonate) alone, or ELF-EMF with MMS in medium. The duration of exposure was 2, 4, 8, 16 and 24 hours. After the exposure, the cells were collected by cell-scraper, washed with PBS, and then we extracted DNA from the cells. After isolating DNA, ARP (Aldehyde Reactive Probe) reagents were added to DNA. Then, AP sites were tagged with biotin residues, which could be quantified using avidin-biotin assay, followed by a colorimetric detection of 450 nm. The number of AP sites were determined by calibration curve of from 0 to 40ARP/10⁵bp in standard DNAs. There was no difference in the number of AP sites between ELF-EMF exposed cells and sham control. The level of AP sites was increased with extending the MMS treatment time. The combined treatment of ELF-EMF and MMS increased AP site levels on 4, 8, 16 and 24 h exposure compared with MMS treatment alone. In this study, the exposure of ELF-EMF alone may have no effect to produce AP site. However, AP sites induced by MMS might be enhanced by ELF-EMF exposure.

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Biological effects of various magnetic fields are not clear in spite of a large number of studies. In a practical sense, there are a number of frequencies and strength of magnetic field in our living environment. Therefore, investigations of biological effects of such complex magnetic fields are required. In this study, effects on cell growth and neurite outgrowth of complex magnetic field with static and 50Hz were investigated using PC12 cell. Cell growth was measured using WST-1 (Roche Diagnostics Co.). 150 µl of cell suspension (5×10⁴ cells/ml) poured in two 96-well plates. One plate was incubated under complex magnetic field with 5T static and 1mT 50Hz components and the other was incubated in conventional incubator. 15 µl of WST-1 solution added to 8 wells and absorption of 415 nm was measured after 3hr incubation following days. Result shows no significant difference on cell growth between complex magnetic field exposure and non-exposure cells. Neurite outgrowth was examined using NS-200 (CHEMICON Int. Co.). Cell suspension was poured into membrane insert for two 12-well plates with RPMI 1640 with 10% FCS, 5% horse serum and NGF (100ng/ml) and plates were treated as cell growth experiment and after 24 hr incubation, cells were fixed with methanol and stained with dye. Neurite outgrowth was estimated by microscopic observation. No significant difference was observed between exposed and control cells. These results show that lack of the biological effects of a complex magnetic field with 5T static and 1mT 50Hz magnetic field.

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Purpose: We have identified the chaperones which regulate radiation-susceptibility (survival capacity and mutability) of human cells and /or human bodies under 1G conditions. The identification has been performed by our established method. In this study, we examined whether the above chaperones, such as GRP94 and GRP78, also regulate cellular response to radiation after exposure of cultured cells to microgravity conditions.
Method: Human RSa cells and their variant cells, HeLa cells and mouse FM3A cells were exposed to microgravity conditions produced by parabolic flight (PF) or free fall (FF) experiment. Before and after the exposure frequency of UVC- or X-ray-induced phenotypic mutation and cellular amounts of chaperones were estimated by drugs (6-thioguanine or ouabain) –resistance tests and by Western blotting analysis, respectively.
Results and Discussion: Decreased capacity of cell survival and DNA repair has been indicated, when cellular amounts of the above chaperones were decreased. The chaperone amounts were decreased in HeLa cells up to 1 h after both exposure. However, the amounts were increased in radiation-resistant variants. On the other hand, after the exposure mutation frequency was decreased in cells tested. Thus, cellular chaperones amounts might be interrelated with refractoriness of cells to radiation.

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Distribution of 137Cs in the western North Pacific Ocean in the water column has been studied for long time since 1960s. The major source of anthropogenic radionuclides in seawater in the Pacific Ocean is global fallout from atmospheric nuclear weapons tests. 137Cs, one of long-lived radionuclides originating from atmospheric weapons tests still exists especially in the upper layers of the Ocean. Concentration data of ¹³⁷Cs are also valuable to establish baselines applicable for dose assessments from consumption of marine food products and for understanding other geochemical processes in the ocean. A core of ¹³⁷Cs concentration in a layer 200-500 m around 20 deg. N is found. In terms of density, it is in a layer sigma 25.0-26.5 with an core center at ca. 26.0. The core of ¹³⁷Cs concentration around 20 deg. N coincides with the density of lighter variety of Central Mode Water (CMW), then this core might formed by subduction of CMW. The concentrations at this core seem to be still increasing. This southward transport process might control longer half-residence time of 137Cs surface water concentration and water column inventory in the equatorial region.

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Plutonium deposition has been continuously observed in Meteorological Research Institute (MRI), Japan since 1958. After 1985, the annual ^239,240Pu deposition in Tsukuba ranged from 1 mBq m^-2 to 10 mBq m^-2, which cannot be explained by stratospheric fallout. Resuspension of ^239,240Pu-bearing soil particles is a candidate of ^239,240Pu source supporting the ^239,240Pu deposition. Recent artificial radionuclide deposition studies reveal that Asian dust, so called "Kosa" is one of origin of ^239,240Pu in recent deposition samples. We present here recent ^239,240Pu deposition observed in Tsukuba and discuss causes of its variation. The annual 239,240Pu depositions in 2001 and 2002 were 7.77 mBq m^-2 and 7.44 mBq m^-2, respectively, which were the highest level during the past 15 years. The annual ^239,240Pu deposition in 2003 decreased to 3.09 mBq m^-2, which was about half of previous years. The monthly ^239,240Pu deposition in 2001 and 2002 showed a marked seasonal variation with a spring maximum. On the other hand, the monthly ^239,240Pu deposition in 2003 showed no clear seasonal trend, although higher ^239,240Pu depositions occurred in February and March. The Kosa events in Japan were remarkable in 2001 and 2002, whereas it was rarely observed in 2003. These findings suggest that the temporal trend of the Asian dust is closely related to that of the ^239,240Pu deposition in Japan.

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¹³⁷Cs, which is of great interest and importance as an indicator of radioactive pollution in marine environments, is one of the long-lived artificial radio-nuclides introduced by the atmospheric deposition of debris from nuclear explosions mainly before 1962. For the estimation of effects of the effluents from nuclear facilities, it is necessary to know the natural variations in the concentration of ¹³⁷Cs and factors affecting variations in marine organisms.
We observed positive correlation between growth and ¹³⁷Cs in 4 species among 14 major teleost species from fishing grounds along the coast of Japan. No increase in ¹³⁷Cs concentration with increase of growth was observed in 2 species. In the remaining species no specific correlation is observed. These differences in the patterns were dependent on a change of food habits with growth. As little is known of the ¹³⁷Cs concentration in teleost we have investigated the natural variations of ¹³⁷Cs in stone flounder. The correlation between growth and the concentration of ¹³⁷Cs in stone flounder will be discussed.

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The fetus is known to be radiosensitive. The increased radiosensitivity of the gonocites with fetal age was reported when pregnant mice were exposed to single doses of X rays. Fetuses are also very sensitive to environmental endocrine disruptors. In the present study, we examined the effects of multiple contamination of tritiated water and vinclozolin, an endocrine disruptors with antiandrogen activity, orally administered to pregnant mouse on the fetus. Pregnant mice were orally administered HTO and vinclozolin at the middle gestation, and tritium concentrations of urine of pregnant mouse, blood and tissues of fetus and placenta and fetul membrane were determined with time until 20 days after the administration. The accumulation doses and biological half lives of HTO in mother mouse and fetus were calculated. Antiandrogenic effects of vinclozolin were also examined.

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