Radiotherapy (RT) is one of the major modalities for the treatment of human cancers and has been established as an excellent local treatment for malignant tumors. Conventional fractionated RT consists of 2-Gy X-rays, fractionated once a day, 5 days a week for 5-7 weeks in total 60 Gy. The efficacy of RT depends on the existence of radioresistant cells, which remains one of the most critical obstacles in RT and radio-chemotherapy. To improve the efficacy of RT, understanding the characteristics of radioresistant cells is one of the important subjects in radiation biology. Several studies have been reported to find out molecules implicated in radioresistance. However, it is noteworthy that cellular radioresistance has been mainly studied among cells with different genetic backgrounds and different origins. Therefore, making a system to compare between radioresistant and sensitive cells with the isogenic background is required. In this review, some aspects of cellular radioresistance mainly focusing on clinically relevant radioresistant (CRR) cell lines that can continue to proliferate even under exposure to 2-Gy X-rays, once a day, for more than 30 days, which is consistent with the conventional fractionated RT are discussed.

Several populations of wild Japanese macaques (Macaca fuscata) inhabit the area around Fukushima Daiichi Nuclear Power Plant (FNPP). To measure and control the size of these populations, macaques are captured annually. Between May 2013 and December 2014, we performed a haematological analysis of Japanese macaques captured within a 40-km radius of FNPP, the location of a nuclear disaster two years post-accident. The dose-rate of radiocaesium was estimated using the ERICA Tool. The median internal dose-rate was 7.6 μGy/day (ranging from 1.8 to 219 μGy/day) and the external dose-rate was 13.9 μGy/day (ranging from 6.7 to 35.1 μGy/day). We performed multiple regression analyses to estimate the dose-rate effects on haematological values in peripheral blood and bone marrow. The white blood cell and platelet counts showed an inverse correlation with the internal dose-rate in mature macaques. Furthermore, the myeloid cell, megakaryocyte, and haematopoietic cell counts were inversely correlated and the occupancy of adipose tissue was positively correlated with internal dose-rate in femoral bone marrow of mature macaques. These relationships suggest that persistent whole body exposure to low-dose-rate radiation affects haematopoiesis in Japanese macaques.

In this study we analyzed the effect of chronic and low-dose-rate (LDR) radiation on spermatogenic cells of large Japanese field mice ( Apodemus speciosus ) after the Fukushima Daiichi Nuclear Power Plant (FNPP) accident. In March 2014, large Japanese field mice were collected from two sites located in, and one site adjacent to, the FNPP ex-evacuation zone: Tanashio, Murohara and Akogi, respectively. Testes from these animals were analyzed histologically. External dose rate from radiocesium (combined Cs andCs) in these animals at the sampling sites exhibited 21 μGy/day in Tanashio, 304-365 μGy/day in Murohara and 407-447 μGy/day in Akogi. In the Akogi group, the numbers of spermatogenic cells and proliferating cell nuclear antigen (PCNA)-positive cells per seminiferous tubule were significantly higher compared to the Tanashio and Murohara groups, respectively. TUNEL-positive apoptotic cells tended to be detected at a lower level in the Murohara and Akogi groups compared to the Tanashio group. These results suggest that enhanced spermatogenesis occurred in large Japanese field mice living in and around the FNPP ex-evacuation zone. It remains to be elucidated whether this phenomenon, attributed to chronic exposure to LDR radiation, will benefit or adversely affect large Japanese field mice.

The effect of the Fukushima Daiichi Nuclear Power Plant (FNPP) accident on humans and the environment is a global concern. We performed biochemical analyses of plasma from 49 Japanese Black cattle that were euthanized in the ex-evacuation zone set within a 20-km radius of FNPP. Among radionuclides attributable to the FNPP accident, germanium gamma-ray spectrometry detected photopeaks only from 134Cs and 137Cs (radiocesium) commonly in the organs and in soil examined. Radioactivity concentration of radiocesium was the highest in skeletal muscles. Assuming that the animal body was composed of only skeletal muscles, the median of internal dose rate from radiocesium was 12.5 μGy/day (ranging from 1.6 to 33.9 μGy/day). The median of external dose rate calculating from the place the cattle were caught was 18.8 μGy/day (6.0–133.4 μGy/day). The median of internal and external (total) dose rate of the individual cattle was 26.9 μGy/day (9.1–155.1 μGy/day). Plasma levels of malondialdehyde and superoxide dismutase activity were positively and glutathione peroxidase activity was negatively correlated with internal dose rate. Plasma alanine transaminase activity and percent activity of lactate dehydrogenase (LDH)-2, LDH-3 and LDH-4 were positively and LDH-1 was negatively correlated with both internal and total dose rate. These suggest that chronic exposure to low-dose rate of ionizing radiation induces slight stress resulting in modified plasma protein and enzyme levels.

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Heat shock protein promoters (hsp promoters) are powerful tools for investigating gene functions, as the expression of targeted genes can be controlled simply by heating. However, there have been no reports of the utilization of an endogeneous medaka (Oryzias latipes) hsp promoter to induce exogenous gene expression in medaka. We identified and cloned a functional medaka hsp promoter (olphsp70.1) and verified its ability to act as an inducible promoter both in vitro and in vivo. The hsp promoter efficiently induced exogenous gene expression in cultured cells, developing embryos, and also in adult fishes. When used to control the expression of Venus, a variant of yellow fluorescent protein, in transgenic medaka, the hsp promoter was functional in all tissues except for the gonads of adults. These results indicate that the medaka hsp promoter can be a powerful tool for inducing exogenous gene expression and investigating gene functions both in vitro and in vivo in medaka.

Radiotherapy (RT) is one of the major modalities for the treatment of human cancer and has been established as an excellent local treatment for malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in RT. To know the characteristics of radioresistant cells, clinically relevant radioresistant (CRR) cell lines were established. CRR cells can continue to proliferate in vitro and in vivo after exposure to 2 Gy/day of X-rays for more than 30 days. Daily microscopic observation of the irradiated CRR cells has indicated that the increase in cell death is not observed within 7 days of irradiation with 10 Gy of X-rays, suggesting that cell death is involved in cellular radioresistance. Radiation-induced regulated cell death (RCD) can be classified into three categories: apoptosis, autophagy-dependent cell death and necrosis (necroptosis). This review focuses on an aspect of radiation-induced RCD that has often been neglected: the manner in which the cells are destroyed. In many studies, apoptosis is considered the primary mode of RCD in irradiated cancer cells; however, it is necessary to consider necrosis or necroptosis as one of the modes of radiation-induced RCD.

It is not an exaggeration to say that, without nuclear accidents or the analysis of radiation therapy, there is no way in which we are able to quantify radiation effects on humans. Therefore, the livestock abandoned in the ex-evacuation zone and euthanized due to the Fukushima Daiichi Nuclear Power Plant (FNPP) accident are extremely valuable for analyzing the environmental pollution, its biodistribution, the metabolism of radionuclides, dose evaluation and the influence of internal exposure. We, therefore, sought to establish an archive system and to open it to researchers for increasing our understanding of radiation biology and improving protection against radiation. The sample bank of animals affected by the FNPP accident consists of frozen tissue samples, formalin-fixed paraffin-embedded specimens, dose of radionuclides deposited, etc., with individual sampling data.