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Since the Fukushima Dai-ichi Nuclear Power Plant (F1-NPP) accident in 2011, radiation effects on wildlife in the contaminated areas have been a major concern. The outskirts of the F1-NPP are mainly rural areas, where many rice fields and streams and reservoirs are located. We searched for wild medaka (small aquarium fish) around the F1-NPPand found 2 wild medaka habitats (S1 and S2). S1 is a stream located 4 km from the F1-NPP, where the ambient dose equivalent rate was 0.4-0.9 μSv/h (2013-14), and S2 is a reservoir located 7.5 km from the F1-NPP, where the ambient dose equivalent rate was 9.8-22 μSv/h (2013-14 and 2017-18). Dosimeters were placed for one day at the locations where the medaka were captured, and the absorbed dose rates were estimated. Radiation effects on wild medaka were examined using micronucleus assay between 2013 and 2018. No significant difference in frequency of micronucleated gill cells was observed among the wild medaka from S1, S2 and our cultivated medaka that were used as a control.

Uncertainties due to confounding factors in epidemiological studies have limited our knowledge of the effects of low dose-rate chronic exposure on human health. Animal experiments, wherein each subject is considered to be nearly identical, can complement the limitations of epidemiological studies. Therefore, we conducted a joint analysis of previously published cancer mortality data in B6C3F1 female mice chronically and acutely irradiated with 137Cs gamma rays to estimate the dose-rate effectiveness factor. In the chronically irradiated animal experiment conducted by the Institute for Environmental Sciences, mice received irradiation at dose rates of 0.05, 1.1 or 21 mGy per day for 400 days from 8 weeks of age. For the acutely irradiated animal experiment conducted by the National Institute of Radiological Sciences, mice received irradiation at 35, 105, 240 or 365 days of age with 1.9, 3.8 or 5.9 Gy at a dose rate of 0.98 Gy per min. Because the preliminary analyses suggested that the risk was dependent on the age at exposure, a model was applied that considered risk differences depending on this factor. The model analysis revealed a three-fold, significantly decreased risk per Gy in mice exposed to 21 mGy per day compared to that in acutely irradiated mice. This resulted in a dose-rate effectiveness factor larger than that reported previously.

Although the risk of breast cancer after high dose rate radiation exposure has been firmly established, the risk incurred by low dose rates is not well understood. Herein, we provide experimental evidence for dose rate and age dependencies induced by continuous γ-ray irradiation on mammary carcinogenesis. Female rats were subjected to continuous whole-body irradiation i) at 7 weeks of age (denoted adults) at a dose rate of 360 mGy/h (4 Gy total) or ii) at 3 weeks of age (denoted juveniles) or as 7-week-old adults at a dose rate of 6 mGy/h (18 Gy total). Additional rats were acutely irradiated at 13 weeks of age at a dose rate of 30 Gy/h (0.5–4 Gy total). We observed the incidence of mammary tumors by weekly palpation until they were 90 weeks old and following pathological inspection upon autopsy. The tumor incidence rate for each group was characterized by Cox regression analysis. When adult rats were irradiated at 60 mGy/h for a total of 4 Gy, their hazard ratio for mammary carcinoma significantly increased relative to unirradiated controls; however, for adult rats irradiated at 3–24 mGy/h, even though they also received a total of 4 Gy, their hazard ratio for carcinoma incidence did not significantly increase. A larger increase in the incidence rate of carcinoma per dose was found for the juveniles than for the adults irradiated at 6 mGy/h, whereas age did not influence the effect of acute irradiation at 30 Gy/h; a threshold-like dose response was observed for irradiation at 6 mGy/h (threshold, ~2.5 and ~4 Gy for juveniles and adults, respectively). Regarding benign tumors of the mammary gland, a significant increase in their incidence was observed for irradiation down to 6 mGy/h, but not at 3 mGy/h, and there was no evidence of age-dependent induction. Thus, induction of female rat mammary carcinogenesis by continuous γ-ray irradiation was age dependent and drastically increased for adult rats between 24 and 60 mGy/h.

Purpose: The aim of this study was to establish a new method of real-time, in vivo detection of radiation damage and recovery. Methods: The thymus was observed under fluorescent light in a green fluorescent protein transgenic medaka. After irradiation, medaka thymus images were analyzed to quantify the effects of radiation by measuring changes in thymus size. A single acute irradiation of X-rays (0–30 Gy) or heavy Fe ions (0–10 Gy) was delivered to the medaka. Images were captured 0, 1, 2, 3, 5, 7, 11, and 21 days after irradiation. Dose-response assessment was conducted to provide a direct measurement of the effects of the radiation. Conclusion: A biomonitoring system to detect the effects of radiation in real time was established. Using this system, the threshold doses for the induction of thymic atrophy by acute X-rays and Fe ions were 2–5 Gy and 0.5–1 Gy, respectively. The Relative Biological Effectiveness (RBE) of Fe-ion to X-rays was estimated to be around 3. This system may be used to evaluate the risk from concurrent exposure to hazards, such as chemicals and radiation, and for aging research.

1. はじめに 放射線防護のためのリスク評価では原爆被爆者の疫学研究の結果が主に用いられているが、低線量・低線量率放射線被ばくによるリスクの定量的評価に直接結びつく放射線影響研究の成果は十分には得られていない。そのため低線量放射線リスクを含む放射線影響・防護に関する情報をまとめて評価し、研究課題を抽出したうえで、解決方策を企画する役割を持つ研究基盤を構築することの必要性が認識されてきた。欧州では、低線量影響研究の研究基盤であるMELODI (Multidisciplinary European Low Dose Initiative)が2009年に設立され、米国でもMELODIの国際連携の呼び掛けに応える形で、IDEA (International Dose Effect Alliance)の構築が提案され、2016年11月に第一回のワークショップがElectric Power Research Institute (EPRI)において開催された。さらに経済協力開発機構/原子力機関(OECD/NEA)は、昨年度から低線量放射線影響研究に関する専門家グループ(HLG-LDR: High-Level Group on Low-Dose Research)を立ち上げ、国際共同研究の支援・調整を担う機能を検討している。量研機構放医研では「放射線リスク・防護研究基盤準備委員会」を2016年に立ち上げ、今後解決すべき科学的研究課題を抽出し、その課題解決のために研究基盤に要求される機能と体制について検討し報告書*としてまとめた。2017年には、放射線防護や低線量放射線影響研究に係る専門家(国内の大学や関連研究機関等を含む)により構成される放射線リスク・防護研究基盤(PLANET)の運営を行う委員会を設置し、活動を継続している。 2. PLANETの活動と本セッションについて PLANETは「動物実験線量率効果検討ワーキンググループ」を設置し、「動物実験における線量率効果検討の基盤となる生物学的メカニズムに係わる文献のレビュー」をまとめると共に、「放医研の単回照射と環境研の連続照射の動物実験データの統合解析」を行っている。国外では、化学物質のリスクを効率的に評価する目的でOECD/NEAを中心に国際的に開発されてきた有害性発現経路(AOP: Adverse Outcome Pathway)を、低線量・低線量率放射線リスク評価に活用する研究も開始された。 本セッションではPLANETの概要と海外における研究基盤の現状の課題を紹介し、次いでワーキンググループの低線量率動物実験データ解析結果と文献レビューの概要、AOPを中心とした国外動向を紹介することにより、低線量・低線量率放射線被ばくによるリスクに関する課題解決に向けた意見交換を広く行いたい。 [参考文献] https://www.qst.go.jp/uploaded/attachment/2910.pdf, 日本保健物理学会第５３回研究発表会

Since the Fukushima nuclear power plant accident, there is an increasing interest in low-dose, long-term radiation exposure in the field of radiation effect research, and epidemiological data using cumulative radiation dose is being analyzed. Cumulative exposure covariates included in statistical models are dependent on the strong and implicit assumption that risks from exposure in the different periods are equal throughout study span. A new approach of weighted cumulative exposure for effect modification was proposed. In this proposed approach, cumulative exposure is considered as a combination of single exposure components in different time periods, and weighted cumulative exposure is calculated as the weighted summation of single doses. Exponential functions were assumed for the weight function and parameters included in the weight function were also estimated with the other parameters in the parameter optimization procedure. The performance of the proposed approach was evaluated through simulation studies and applied to a long-term cohort study of cancer mortality among female nuclear weapons workers. Based on the results of simulation studies, it was suggested that the proposed approach was almost unbiased in the situation where the sample size exceeds 1000 and the change in sensitivity is monotonous. When the approach was applied to female nuclear worker data, a slight decreasing trend in breast cancer risk with increasing age at exposure was observed., The 4th International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science

乳がんは、高線量率の放射線被ばく後に、リスクの増加が鋭敏に検出される病気の一つである。我々は最近、ラットを用いた連続γ線照射実験によって、どのような線量率で乳がんのリスクが高くなるか、思春期前後の年齢でそのリスクが異なるかどうかを調べ、年齢別の線量率効果係数を推定した（Imaoka et al. Radiat Res 191, 245–254, 2019）。本稿では、その研究の概要を紹介したい。

広島・長崎の原爆被爆者を対象とした寿命調査のデータは、放射線リスクの評価や放射線防護基準の策定に重要な役割を果たしている。放射線リスク研究において避けられない線量推定誤差の問題にも膨大な労力が割かれており、放射線疫学研究の中で最も信頼のできる研究の一つとして、得られた知見は世界中で広く利用されている。一方で福島原子力発電所の事故以来、低線量の長期被 ばくのリスクに対する関心が高まっており、長期の低線量の放射線を受けた集団の疫学研究結果が注目されている。一般に放射線疫学のコホート研究では、対象者の様々な背景因子を調整するためにポアソン回帰や Cox 回帰などのモデルを用いた解析が主流であり、低線量長期コホート研究において線量は一定時点までの線量を累積した累積線量が用いられる。しかしながら、そのような累 積線量を用いた解析には、被ばくした時点に依らずそのリスクは一定であるという暗黙の仮定が含まれている。被ばく時年齢によって放射線感受性は変化することが原爆被爆者の疫学研究の結果から示唆されており、長期に渡って曝露を受けるコホートにおいて被ばく時年齢による効果の修飾を考慮できないことは問題である。そこで本研究ではox 回帰における時間依存性共変量の枠組み にて、重み付き累積線量を用いる手法を提案した。提案手法では、各時点における線量の重み付き和として計算され、重み関数には被ばく時年齢の一次式を含む指数関数を仮定した。重み関数のパラメータは他のパラメータと同様に非線形最適化関数によって推定される。提案した手法は、シミュレーション研究によって性能を評価した後、核兵器開発施設における女性作業者の放射線疫学データに適用した。シミュレーション研究の結果、対象者数が 1000 を越え、また被ばく時年齢による放射線感受性が単調に変化する状況では提案手法はほぼバイアスがないことが示唆された。核兵器開発施設における女性作業者のデータに適用したところ、線量あたりの乳がん死亡率は被ばく時年齢の増加と共 に僅かに減少する傾向を示し、被ばく時年齢 60 歳における 10 mSv あたりの死亡率のベースラインに対する増加は、従来の手法では 0.060 であった一方で、提案手法では 0.054 となった。, 2019年度統計関連学会連合大会

Childhood exposure to ionizing radiation (IR) and daily secondhand smoke increases the risk of developing lung cancer. Assessment of risks associated with childhood exposure to IR when combined with chemical carcinogens is of great importance. We studied the age dependence of the effect of combined exposure to IR and a chemical carcinogen on lung carcinogenesis. Female 1-, 5-, and 22-week-old Wistar rats were locally irradiated on the thorax with X-rays (3.18 Gy) and/or were injected intraperitoneally with N-nitrosobis(2-hydroxypropyl)amine (BHP) (1 g/kg body weight) 1 week after X-ray exposure or at 23 weeks of age. Rats were sacrificed at 90 weeks of age. We found that: (i) the incidence of lung tumors (both adenomas and adenocarcinomas) increased as a function of the age at X-ray exposure, whereas it decreased with age after BHP administration; (ii) combined exposure to X-rays at 5 or 22 weeks with BHP 1 week later promoted adenomas and adenocarcinomas; (iii) although a longer interval between the X-ray and BHP treatments reduced the combined effect, carcinogenic events of early-life irradiation at 1 or 5 weeks of age lasted into adulthood; (iv) most tumors originated from surfactant apoprotein A-positive alveolar type II cells; and (v), extracellular signal-regulated kinase pathway activation was observed in half the adenocarcinomas, regardless of the exposure schedule. Lung carcinogenesis following IR and BHP exposure is dependent on age-atexposure. Combined exposure to X-rays and BHP promoted lung tumorigenesis, especially malignant tumors, for all ages of irradiation.

Purpose: The risk of developing secondary cancer after radiotherapy, especially after treatment of childhood cancers, remains a matter of concern. The high biological effects of carbon-ion radiation have enabled powerful radiotherapy, yet the approach is commonly restricted to the treatment of adults. Susceptibility of the fetus to particle radiation-induced cancer is also unclear. The present study is aimed to investigate the effect of carbon-ion irradiation in childhood on breast carcinogenesis. Methods and Materials: We irradiated female Sprague-Dawley rats of various ages (embryonic days 3, 13 and 17, and 1, 3, 7 and 15 weeks after birth) with 137Cs gamma rays or a 290-MeV/u monoenergetic carbon-ion beam (linear energy transfer, 13 keV/um). All animals were screened weekly for mammary carcinoma by palpation until they were 90 weeks old. Results: Irradiation of fetal and mature (15-week-old) rats with either radiation source at a dose of 0.2 or 1 Gy did not substantially increase the hazard ratio compared to the non-irradiated group. Dose responses (0.2-2.0 Gy) to gamma rays were similar among the groups of rats irradiated 1, 3 and 7 weeks after birth. The effect of carbon ions increased along with the age at the time of irradiation, indicating relative biological effectiveness values of 0.2 [-0.3, 0.7], 1.3 [1.0, 1.6] and 2.8 [1.8, 3.9] (mean and 95% confidence interval) for animals that were 1, 3 and 7 weeks of age, respectively. Conclusions: Our findings imply that carbon-ion therapy may be associated with a risk of secondary breast cancer in humans, the extent of which may depend on the age of the patient at the time of irradiation.

To characterise indirect effects of ionising radiation on aquatic microbial communities, effects of acute gamma-irradiation were investigated in a microcosm consisting of populations of green algae (Chlorella sp. and Scenedesmus sp.) and a blue-green alga (Tolypothrix sp.) as producer; a ciliate protozoan (Cyclidium glaucoma), rotifers (Lecane sp. and Philodina sp.) and an oligochaete (Aeolosoma hemprichi) as consumer; and more than four species of bacteria as decomposers. Population changes in the constituent organisms were observed over 160 days after irradiation. Prokaryotic community structure was also examined by denaturing gradient gel electrophoresis (DGGE) of 16S rDNA. Principle response curve analysis revealed that the populations of the microcosm as a whole were not significantly affected at 100 Gy while they were adversely affected at 500-5000 Gy in a dose-dependent manner. However, some effects on each population, including each bacterial population detected by DGGE, did not depend on radiation doses, and some populations in the irradiated microcosm were larger than those of the control. These unexpected results are regarded as indirect effects through interspecies interactions, and possible mechanisms are proposed originating from population changes in other organisms co-existing in the microcosm. For example, some indirect effects on consumers and decomposers likely arose from interspecies competition within each trophic level. It is also likely that prey-predator relationships between producers and consumers caused some indirect effects on producers.

Ecosystems consist of various organisms, and there are complex interactions among these organisms. Indirect effects through interspecies interactions should be considered as well as direct effects of ionising radiation when environmental effects are evaluated. We therefore began to investigate radiation effects on experimental model ecosystems, i.e., microcosms mimicking aquatic microbial communities. The microcosm used in this study consisted of green algae (Chlorella sp. and Scenedesmus sp.) and blue-green alga (Tolypothrix sp.) as producers; oligochaete (Aeolosoma hemprichi), rotifers (Lecane sp. and Philodina sp.) and ciliate protozoa (Cyclidium glaucoma) as consumers; and four or more species of bacteria as decomposers. The steady-state microcosm was acutely irradiated with 60Co gamma-rays at 100, 500, 1000 and 5000 Gy, and population changes were observed for 25 days. In the control microcosm, population densities of the constituent organisms were almost constant during the experiment. At 100 Gy, significant effects were not observed for any organisms. At 500 Gy, A. hemprichi died out. Green algae and bacteria were not affected until day 15, but were decreased on day 25. C. glaucoma was temporarily decreased just after irradiation, but the cell density was recovered to a control level on day 7. Tolypothrix sp. was not affected until day 15, but was increased on day 25. Rotifers were not affected. At 1000 Gy, A. hemprichi died out. Bacteria were decreased just after irradiation, and the cell density remained slightly lower than controls during the experiment. Chlorella sp. and Scenedesmus sp. were not affected until day 15 and 10, respectively, but were decreased thereafter. C. glaucoma was temporarily decreased just after irradiation, but the cell density was recovered to a control level on day 10. Tolypothrix sp. was not affected until day 15, but was increased on day 25. Rotifers were not affected. At 5000 Gy, A. hemprichi, Lecane sp., and C. glaucoma died out. Bacteria were decreased just after irradiation, and the cell density remained significantly lower than controls during the experiment. Green algae were not affected until day 10, but were decreased thereafter. Tolypothrix sp. was not affected until day 15, but was increased on day 25. Philodina sp. was not affected. Most of observed effects were adverse, and were generally depended on radiation doses. But Tolypothrix sp. was increased at 500 Gy or higher doses. It is thought that this unexpected result arose from indirect effects. In the irradiated microcosm, decrease in green algae might provide Tolypothrix sp. with an advantage in the competition for light and inorganic nutrients. Breakdown products such as CO2 and inorganic nutrients originated from dead organisms might also contribute to increase in Tolypothrix sp. Equi-dosimetric analysis will be carried out between gamma-rays and some chemicals. That is, effective radiation doses evaluated in this study will be quantitatively compared with effective concentrations of herbicides (simazine and thiobencarb), surfactants (LAS and soap) and copper, which had been evaluated in other studies., International Conference on Radioecology and Enviornmental Radioactivity

The photostability of Rhodamine 6G is of crucial importance for the organic light-emitting display of mobile phones. Photobleaching of Rhodamine 6G in acetone was not protected by β-carotene, but was efficiently photostabilized by t-butyl hydroxyanisole. The results indicate that photobleaching of Rhodamine 6G in acetone was not caused by singlet oxygen but some radical species.

Lung cancer has been associated with high doses of radiation. Studies of populations with low, protracted exposures have provided little or inconsistent evidence of a dose-response, possibly due to difficulty in taking into account the effect of cigarette smoking, which may confound or interact with radiation exposure. While the joint effect of radiation and smoking has been well investigated in several studies, there is limited information about the joint effect of chronic low LET radiation exposure and smoking. We examined lung cancer mortality risk among 106,029 US radiologic technologists who were cancer-free at a baseline questionnaire with follow-up from the baseline questionnaire until the end of 2007. The average follow-up was 20.7 years and there were 843 lung cancer deaths. Cumulative lung doses (mean 0.017, range 0-0.81Gy) were estimated using a Monte Carlo dosimetry system. Poisson regression models for excess relative risk (ERR) were employed to examine the joint effect of radiation and smoking, adjusted for age, sex, birth year and race. Multiplicative and additive interaction forms were compared using the AIC. An ERR model with additive interaction fit best. The ERR per Gy for lung cancer mortality was estimated to be 10.94 (-2.57, 24.46) and the ERR per 20 pack-years of cigarettes smoked, 1.10 (0.41, 1.79)., 日本放射線影響学会第56会大会

The risk of developing secondary cancer after radiotherapy, especially after treatment of childhood cancers, remains a matter of concern. The high biological effects of carbon-ion radiation have enabled powerful radiotherapy, yet the approach is commonly restricted to the treatment of adults. The present study is aimed to investigate the effect of carbon-ion irradiation in childhood on breast carcinogenesis. We irradiated female Sprague-Dawley rats of various ages (embryonic days 3, 13 and 17, and 1, 3, 7 and 15 weeks after birth) with 137Cs gamma rays or a 290-MeV/u monoenergetic carbon-ion beam (linear energy transfer, 13 keV/um). All animals were screened weekly for mammary carcinoma by palpation until they were 90 weeks old. Irradiation of fetal and mature (15-week-old) rats with either radiation source at a dose of 0.2 or 1 Gy did not substantially increase the hazard ratio compared to the non-irradiated group. Dose responses (0.2-2.0 Gy) to gamma rays were similar among the groups of rats irradiated 1, 3 and 7 weeks after birth. The effect of carbon ions increased along with the age at the time of irradiation, indicating relative biological effectiveness values of 0.2 [-0.3, 0.7], 1.3 [1.0, 1.6] and 2.8 [1.8, 3.9] (mean and 95% confidence interval) for animals that were 1, 3 and 7 weeks of age, respectively. Our findings imply that carbon-ion therapy may be associated with a risk of secondary breast cancer in humans, the extent of which may depend on the age of the patient at the time of irradiation., Heavy Ion in Therapy and Space Radiation Symposium 2013

There are some R packages which uses GPU for computation, and the better performance is provided by GPU-equipped computers. However, the current number of implemented functions in their packages is limited because special procedures are required for utilization of GPU, such as memory allocation in video memory, and data transfer between main memory and video memory. Furthermore, these packages are not easy to use for Windows users because binary packages are not provided, and it is not easy for Windows users to build a developing environment. Since there seems to be a large number of potential Windows users, it is beneficial to develop a package which enables GPU computing easily on Windows. Therefore, we began to develop a new package which utilize GPU in computation with minimum modification of R source code, and also can be used easily for Windows users. The package development is ongoing, and the detail specifications are not fixed, except that the package is developed with NVIDIA's CUDA toolkit. Our package CUtil (CUDA Utility package) will be equipped with the following features. As described above, the first feature is that Windows users will be able to use this package easily. This package will be available from CRAN, and we will also try to make Windows binary packages available. The second feature is that after loading the package, the frequently used operators and functions can be overridden. With this overriding, we can enjoy GPU computation performance with minimum modification of R source code. The third feature is that the package minimize the data transfer cost between main memory and video memory. The data on video memory is treated as external pointer in R objects, and once the R object on main memory is transferred to video memory for GPU computation, the data is kept on video memory as R objects. The next time of the GPU computation, the data can be used directly by GPU without the data transfer. Because it is known that the proportion of time needed for the data transfer is relatively high, this advantage will be beneficial especially for a long series of computations, such as Markov chain Monte Carlo methods in Bayesian statistics. Other than these features, we are going to implement double precision floating-point and complex number computation in addition to single floating-point, and garbage-collection, which enables us to use a small amount of video memory effectively. This package will require computers with NVIDIA's GPU (compute capability is equal to or greater than 2.0)., The R User Conference 2011

Introduction: Cancer risks following radiotherapy have not well characterized in terms of radiation dose while radiotherapy is recognized as an established risk factor. In our previous meta-analysis of second cancer risks among children who received radiotherapy, the small number of eligible studies precluded detail evaluations. In the current meta-analysis, we developed and applied a method to calculate an ERR estimate from another form of estimates. Methods: We have developed the method to estimate the ERR estimates from the studies in which the relative risk estimates per several dose categories, such as odds ratio, hazard ratio, incidence rate ratio, are available. We fit a linear regression model including radiation dose as a covariate and regard the slope as an ERR estimate. For the estimation of standard error of the ERR estimate, we used the bootstrap method. The overall ERR estimates of radiotherapy were calculated using a random effects model. To validate our method, we compared the ERR estimates from our calculation and from literature where both ERR and the relative risk estimates per several dose categories are available. Results: A total of 23 studies were identified as eligible for meta-analysis through search of PubMed database. ERR estimates were available in 12 studies, and for the rest 11 studies, we calculated a ERR estimate from other estimates. The ERR estimates ranged from 0.004 to 11.7 with the overall ERR of 0.44 (95%CI: 0.22, 0.85), which was far smaller than the corresponding estimate of 1.7 from the study of atomic bomb survivors exposed as young children. Heterogeneity was suggested by Cochran's Q statistics (Q=209, DF=23, p, 2010 American Statistical Association Conference on Radiation and Health

We have conducted a meta-analysis of studies on the excess relative risk per Gy (ERR) of second cancer before, but the small number of eligible studies restricted quantitative evaluations. To solve this problem, a method to calculate ERR per Gy estimates from another form of estimates was developed, and a meta-analysis was conducted again. We searched the PubMed database, and 26 studies were identified. ERR per Gy estimates were available in 15 studies, and for rest 11 studes, we used the regression model to calculate ERR per Gy estimates from other estimates. The overall ERR per Gy estimate was 0.61 (95% CI: 0.31, 1.2), which was much lower than that of atomic bomb survivors exposed as young children (1.7; 95%CI: 1.1, 2.5). Heterogeneity of the ERR per Gy estimates among studies was suggested, and the reasons were explored. It was suggested that ERR per Gy estimates in the different SMN sites differed greatly, and they also decreased to 0.88 time by one year increase in primary cancer age. The heterogeneity could be explained by the SMN sites and primary cancer age to some extent., The Third Asian and Oceanic Congree on Radiation Protection

Cancer risk of children following low-dose irradiation is of great concern, especially with rapid increases in diagnostic use of radiation. However, the accurate risk assessment for low-dose radiation poses many challenges. This is partly due to the inability to distinguish radiation-induced tumors from spontaneous tumors. In this study, we analyzed the dose-dependent effect of radiation on medulloblastoma development in newborn Ptch1 heterozygous mice. The incidence increased, and the latency decreased as a function of dose. Loss of heterozygosity (LOH) at Ptch1 locus in spontaneous tumors extended to telomeric regions (S-type) on chromosome 13, which was probably mediated by mitotic recombination. In contrast, tumors developed after 3 Gy irradiation exhibited interstitial deletion around Ptch1 (R-type). There was a clear dose-dependence in the proportion of R-type tumors at intermediate doses, suggesting R-type as a reliable radiation signature. R-type tumors increased significantly even at 50 mGy, strongly suggesting that low-dose radiation, indeed, contributes to tumorigenesis. Integrated array-CGH and expression microarray analyses demonstrated that expression levels of many genes on chromosome 13 faithfully reflected the signature-associated genomic copy-number reduction around Ptch1 locus. Interestingly, the signature was also connected with expression of many genes on chromosomes other than chromosome 13, including Tgfb2, Pax6 and Plagl1/Zac1, which play pivotal roles and change expression levels in the early development of cerebellar granular precursor, an origin for medulloblastoma. These findings of genome and transcriptome signatures of radiation will provide novel insights into cancer risk assessment for low-dose radiation, and the possible discriminative property of radiation carcinogenesis such as an early onset., Keystone Symposia: Integration of Developmental Signaling Pathways

Background: Cancer risks following radiotherapy have not been well characterized in terms of radiation dose. Before we have conducted a meta-analysis of studies on the excess relative risk per Gy (ERR) of second malignant neoplasm (SMN) among childhood cancer survivors, but the small number of eligible studies restricted quantitative evaluations. To solve this problem, we developed a statistical method to calculate an ERR estimate from other estimates, and conducted a meta-analysis again. Materials and Methods: We searched the PubMed database, and 21 studies were identified. ERR estimates were available in 10 studies, and for the rest 11 studies, we used the regression-based model to calculate a ERR estimate from other estimates. The overall ERR estimates of radiotherapy were calculated using a random effects model. Results and Discussion: The ERR estimates from 21 studies ranged from 0.004 to 11.7. The overall ERR was 0.45 (95%CI: 0.21, 0.97), which was far smaller than the corresponding estimate of 1.7 from the study on atomic bomb survivors exposed as young children. Heterogeneity was suggested by Cochran's Q statistics (Q=188, DF=20, p, WHO satellite meeting "Radiation risk assessment in pediatric healthcare" in KIDS Workshop 2009 in NIRS

Cancer risks of low-dose radiation are of great concern especially in relation to rapidly increasing medical exposures; however, their accurate assessments cope with many challenges and difficulties, partly due to inability to distinguish radiation-induced tumors from spontaneous ones. Here, we analyzed dose-dependent effect of radiation on medulloblastoma development in Ptch1 heterozygous mice on C3B6F1 background. The incidence and latency of medulloblastoma increased and shortened with increasing radiation dose, respectively (Fig. 1). Amazingly, radiation contributed tumorigenesis even at 50 mGy and 100 % of mice got medulloblastoma with 1.5 Gy. Loss of heterozygosity (LOH) analysis on a total of 164 tumors (Fig. 2) indicated that spontaneous tumors showed LOH in broad regions on chromosome 13, including Ptch1 and distally-extending telomeric portion (S-type). In contrast, tumors developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 (R-type). A clear dose-dependent increase in the proportion of R-type tumor at intermediate doses suggested R-type to be a reliable radiation signature (Fig. 3). Array-CGH analysis indicated the R-type-specific copy-number reduction around Ptch1 and LOH-type-independent frequent gains of whole chromosome 6. Integrated expression microarray analysis indicated that expression levels of many genes within the altered genomic regions faithfully reflected the genomic copy-number changes. Furthermore, it was also suggested that these expression changes in turn influenced on many other genes, such as Tgfb2 and Plagl2, on widespread genomic regions. This is the first demonstration that radiation-induced tumors developed after low-dose irradiation can be characterized quite precisely by interstitial deletion of Ptch1 and by associated gene expression profile., KIDS workshop 2009 in NIRS - IAEA NIRS Joint Workshop & NIRS Symposium on Radiation Protection for Children

In most countries, radon is the dominant contributor among natural radiation sources to the radiation exposure dose of the general population. Many studies of underground miners have consistently demonstrated that exposure to high levels of radon gas and its decay products increase the risk of lung cancer, and the radon progeny are now a well-recognized cause of lung cancer. Since radon is found in homes and is also present outdoors although the concentration is lower outside, numerical case-control studies of residential radon and lung cancer have been conducted using passive radon (Rn-222) detectors. These studies showed that radon may increase lung cancer risk, but most of them did not show a significant risk. Recently it was shown that the readings of passive radon detectors that do not employ thoron (Rn-220) discrimination techniques are affected by thoron. Therefore, we conducted a simulation study to evaluate the possible effect of thoron interference on the estimation of radon-related lung cancer risk. Various assumptions were made based on the number of cases, matching ratio, baseline risk, true radon-related risk, distribution of radon and thoron concentrations, correlation between radon and thoron, and radon detectors. The results suggested that in certain circumstances thoron interference in radon measurements resulted in an approximately 90% downward bias. In addition, the magnitude of the bias increased as the geometric mean and geometric standard error of radon concentration decreased and those of thoron increased. In order to resolve this problem, it is necessary to use passive radon detectors with thoron discrimination techniques in epidemiological studies., The First Meeting for the International Joint Research on Construction of Natural Radiation Exposure Study Network