In the northern part of Japan, close cooperation is essential in preparing for any possible emergency response to radiation accidents because several facilities, such as the Low-Level Radioactive Waste Disposal Facility, the MOX Fuel Fabrication Plant and the Vitrified Waste Storage Center, exist in Rokkasho Village (Aomori Prefecture). After the accident at Fukushima Daiichi Nuclear Power Plant in 2011, special attention should be given to the relationship between radiation and human health, as well as establishing a system for managing with a radiation emergency. In the area of Hokkaido and Aomori prefectures in Japan, since 2008 an exchange meeting between Hokkaido University and Hirosaki University has been held every year to have opportunities to discuss radiation effects on human health and to collect the latest news on monitoring environmental radiation. This meeting was elevated to an international meeting in 2014 titled “Educational Symposium on Radiation and Health (ESRAH) by Young Scientists”. The 3rd ESRAH meeting took place in 2016, with the theme “Investigating Radiation Impact on the Environmental and Health”. Here we report the meeting findings on the continuing educational efforts after the Fukushima incident, what was accomplished in terms of building a community educational approaches, and future goals.
INTRODUCTION
Ionizing radiation has the potential to affect human tissues by energy deposition, causing mutation, cell death and cancer induction, via mainly DNA damage (1). By taking advantage of positive aspects of radiation (high permeability and energy convergence), not only image diagnosis but also radiotherapy have been achieved. However, damaging effects on normal tissues cannot be ignored from a radiation protection stand point. After the accident at Fukushima Daiichi Nuclear Power Plant (F1-NPP) following the earthquake and tsunami on March 11, 2011, large amounts of artificial radionuclides were released (2). This incident has focused close attention to human health after low-dose and low-dose-rate exposure (3). In the northern part of Japan, several facilities, such as the Low-Level Radioactive Waste Disposal Facility, the MOX Fuel Fabrication Plant and the Vitrified Waste Storage Center, exist in Rokkasho Village in Aomori Prefecture (4, 5). Close cooperation in this area is therefore crucial in preparation for any emergency radiation accidents. Young researchers and radiologists have the responsibility to ensure future human safety by investigating the relationship between ionizing radiation and human health.
For learning, precisely what effects radiation has on human health, it is important to provide the opportunity to share knowledge among specialists on radiation study. To provide this opportunity for young researchers, an idea exchange meeting between Hokkaido University and Hirosaki University has been held every year since 2008. After the accident at F1-NPP, in 2014 this meeting was elevated to an international meeting titled “Educational Symposium on Radiation and Health (ESRAH) by Young Scientists” (6). The topic of the meeting was “radiation and human health”, and the 1st and the 2nd ESRAH were held in Hirosaki, Japan in 2014 and 2015 (6, 7). The meeting contributed to not only elevating the knowledge of radiation effects on human health but also establishing a network in the northern part of Japan, envisaging the construction of a radiation emergency system applicable to the whole world.
In 2016, the 3rd Educational Symposium on Radiation and Health by Young Scientists (ESRAH2016) was held on the theme of “Investigating Radiation Impact on the Environment and Health”. At this meeting, three educational lectures and five invited top-class researchers gave talks, and more than 20 poster presentations by graduate students and young investigators were given. Here, we report on the achievement of the ESRAH2016 meeting. The activity through the meeting encouraged the participants to learn about the impact of radiation and to guide the direction of research in this field of study.
Educational Lectures and Invited Talks
Overview of Educational Lectures and Invited Talks. Current topics concerning the relationship between radiation and human health were discussed by eight top-class researchers from three main viewpoints (Fig. 1):
1. Radiation-dose monitoring of radionuclides.
2. Effects of radiation on bio-tissue.
3. Mutual sharing of information on radiation effects.
FIG. 1.
Main three topics on radiation impact on human health: the information was obtained from the educational lectures and the invited talks from eight top-class researchers in this meeting.
The titles of the lectures and talks are summarized in Table 1. The current state of the latest research on radiation was well presented in the lectures and talks.
TABLE 1
List of Educational Lecture (EL) and Invited Talk (IT)
Monitoring Radiation Dose in the Environment
Skills for monitoring radiation dose in the environment due to an accident at a nuclear power plant and of naturally occurring radioactive material (NORM) were introduced by Drs. K. Kelleher and T. Kovács. The focus of Dr. Kelleher's lecture was on the topic of “radiation monitoring” and “lessons learned from nuclear accidents”. Kelleher showed the activity of radionuclides after three radiation accidents: the Windscale Fire (1957), the Chernobyl Accident (1986) and the Fukushima Accident (2011). Based on experiences from these accidents, Dr. Kelleher indicated that two actions are necessary in preparation for the nuclear accident: 1. Maintaining expertise and 2. Developing rapid assessment methods. Dr. Kovács proposed biomonitors (sensitive indicators) such as tobacco plant, which can realize the long-term controlling of the environmental and health effects of depositories (8, 9).
Biological Effects of Radiation on Tissue
Biological effects after exposure to radiation were discussed by Dr. J. Kildea, Dr. N. Autsavapromporn and Dr. T. Tippayamontri, with regards to radiobiology, dosimetry, Monte Carlo modeling and radiotherapy. Dr. Kildia talked about neutron-induced carcinogenic effects (NICE) featured by the energy spectrum (10). In this regard, Dr. Kildea proposed a method to quantify the carcinogenetic risk (biological damage) by a combination of energy spectra measurement and Monte Carlo modeling. Dr. Autsavapromporn presented findings on the mechanism to induce non-targeted effects (NTEs) by using microbeam experiments. Microbeam experiments show that NTEs may contribute to secondary cancer risks in cancer survivors (11, 12). From the view point of clinical practice, Dr. Tippayamontri talked about a method to treat cancer in consideration of the exposure of normal tissue to radiation in radiotherapy. To deliver the appropriate dose to cancer cells without affecting healthy cells, Dr. Thippayamontri showed an approach by using a targeted radionuclide therapy with a combination of 18F-radioisotope (protective to healthy cells) and 5FU (enhancing radiosensitivity in cancer cells) (13–16). The damage effect on normal tissue is also considered under the enhancement of cell killing in tumors.
Sharing Information on Radiation Effects
The importance of sharing correct information on radiation effects and the appropriate management of the nuclear waste was presented by Drs. M. Akashi, T. Kozaki and E. Fidanchevski. Dr. Akashi talked about “Lack of Knowledge and Misunderstandings of Radiation Effects among Health Care Providers”. At the current time, there are a lot of misunderstandings concerning radiation exposure (17). Dr. Akashi strongly recommended that young scientists share the following information on radiation effects: 1. Exposure to radiation alone does not induce immediate death even when a very high dose is received (18); 2. Emergency workers can safely transport contaminated patients to hospital (19); and (3) Symptoms/signs usually do not appear in internal contamination (20). Dr. Kozaki showed us how to manage nuclear waste in Japan. It was also suggested that long-term educational activities are essential to manage nuclear waste. To put it into practice, Dr. Kozaki proposed that the open course is a useful tool for nuclear waste management (21, 22). Dr. Fidanchevski introduced an activity called “NORM4BUILDING COST Action”, which has the potential to improve radiological impact assessment models for the reuse of NORM residues in building materials, which is being conducted in Europe.
Through these lectures, the participants will be able to recognize the lack of knowledge and misunderstandings of radiation effects on health care providers before making an attempt to establish a radiation emergency plan.
Poster Presentations by Young Scientists
Overview of the poster session. There were twenty posters presented, consisting of 11 posters on radiation biology, 3 on medical treatment, 2 on the Fukushima nuclear power plant accident and 4 on radiation measurement (Fig. 2). A one minute oral summarizing presentation was given by each young scientist. The details of the research subjects are summarized in Table 2. During the 90-min discussion period, enthusiastic arguments between the presenters and audience were made, encouraging various new findings. At the closing ceremony of the symposium, poster prizes were awarded to two poster presentations, which were judged by the educational lecturers, the invited speakers and seven teaching staff.
TABLE 2
List of Poster Presentation by Young Scientists
The poster session provided an exciting opportunity for young researchers and students. In the following sections, we outline the contents of the presentations and discussion.
Evaluation of Dose in the Environment and Animals after Nuclear Accidents
To monitor the activity concentration of radionuclides (such as 137Cs, 134Cs, 90Sr or radon) and the dose in the environment or in a solid sample such as tissue, several approaches have been performed after nuclear accidents.
Methods for monitoring radiation of radon progeny, 90Sr, 137Cs and 134Cs from samples such like soil or animal (human) tissue were developed. For example, a new method that is suitable for monitoring the radiostrontium activity concentration in a solid sample was presented by one group in Hungary, which may contribute to monitoring internal exposure after radiation accidents. In Japan, a group investigated the internal contamination of radioactive-cesium (137Cs and 134Cs) associated with the Fukushima Daiichi Nuclear Power Plant (F1-NPP) in the genital tissue of animal (Felis silvestris catus) which were protected by volunteers in Namie Town, Fukushima. However, there is no correlation between internal contamination level and air dose rate (or radioactive-cesium concentration in soil). The problem is not solved at current status. Further, in Angola, the first investigation of dosimetry was performed, and the results reveal that the annual indoor radon activity concentrations in 14% of Angolan adobe houses are expected to have higher values than the WHO reference.
Looking toward biological evaluation, quantifying the pathological condition of tissue after exposure is essential in anticipation of accidental exposure to high-dose ionizing radiation (23, 24). Another group in Japan focused on microRNAs (miRNAs) that have recently emerged as biomarkers for predicting and diagnosing various pathological conditions by identifying the serum miRNA signature. It was suggested in this study that the serum miRNA may serve as a functional dosimeter and early-assessment biomarker of radiation-induced damage to monitor the dose in tissue after accidents.
Apparently, the interests of young investigators have been turned in radiation biology rather than the aftermath of F1-NPP accident as shown in Fig.2.
Approaches for Analyzing Biological Effects after Exposure
Effects of radiation were evaluated from many viewpoints, such as electron-track simulation, biological experiments, mathematical modeling and so on. The impact of radiation on bio-cells (i.e., a series of events to induce cell death) was discussed during the poster presentations.
DNA damage can be induced when the spatial distribution of energy deposition along the secondary electron track (25) is coincident with DNA location in the cell nucleus. A group presented an approach to evaluate the path length of an electron track in relation to the induction of DNA damage, i.e., DNA double-strand breaks (DNA-DSBs) causing fatal DNA damage (26–29). The damage depending on the cell cycle was investigated by incorporating the experimental DNA concentration into a mathematical formula. The cell killing was also evaluated by using a mathematical model in consideration of both targeted effects (energy deposition to cell nucleus) mentioned above (30) and nontargeted effects (not only low-dose hyper-radiosensitivity but also medium transfer bystander effects).
The cellular mechanism after exposure is, however, still unclear from the view point of biological experiments. The behavior of hyaluronan (HA) and CD44 expression (radioresistance) in prostate cancer cell lines exposed to X rays was investigated by a group from Hirosaki University, Japan. An increase of HA in cancer cells after irradiation may be involved in clonogenic potencies. Intriguingly, the interleukin 6 (IL-6) signaling pathway is associated with an acquisition of radioresistance in cancer stem cell-like cells that express CD133. IL-6 is known as one of the signaling pathways of the bystander effect (nontargeted effects) (31). It is possible that the HA is linked to the bystander effect and signal-induced radioresistance (32, 33). On the provision of accidental high-dose exposure, a group tried to establish the transplantation of double-unit umbilical cord blood cells (dUCBCs) (33), which can be used to reconstitute the hematopoietic system. Especially, they focused on the use of an allogeneic UCBC source in dUCBC transplantation that does not require major histocompatibility complex compatibility for treatment in response to a radiation emergency. A project to establish a method to treat patients after accidental radiation exposure is underway.
It is likely that quantitative models can reproduce bio-responses such as DNA damage or cell-killing after irradiation. However, the cellular response including the signals after low-dose exposure still remains to be clarified. Further investigations will be necessary by the experimental approach and also by the construction of theoretical models to interpret the bio-response after irradiation.
Summary and Future Prospects
In 2016 the3rd ESRAH was held, this meeting suggested the direction of research interests mainly for the sake of young scientists and seemed to provide a valuable experience to the participants in a variety of radiation-related research fields, such as dosimetry, management of radiation, biological experiments, theoretical models, Monte Carlo simulations and so on. As a remarkable achievement, young scientists recognized their study phase, in which the knowledge or information about the effects of radiation on tissue (mainly cellular mechanisms) is still insufficient while the data related to biological response and the environmental dose are being gathered little by little after accidents such as F1-NPP. A comprehensive study including biological experiments and theoretical analyses will be effective to evaluate the impact of radiation on human health.
ESRAH is planned to take place every year, ESRAH2017, is scheduled to be held in Hirosaki city, under the direction of Prof. Yoichiro Hosokawa of Hirosaki University, Japan. We are expecting the participation of many radiation researchers. Finally, we express our gratitude to the eight scientists who accepted our offer to give the educational lectures and invited talks.
Funding
This conference was financially supported by HITACHI-GE NUCLEAR ENERGY, LTD., J-MAC SYSTEM, INC and CHIYODA TECHNOL CORPORATION, SAPPORO. In addition, this conference was powered by the grant ‘Strategic Theme 3: “International Education and Research Project based for Safety & Security on Radiation Medicine”, Hirosaki University'. Funding to pay the Open Access publication charges for this article was provided by Hiroyuki Date (Faculty of Health Sciences, Hokkaido University).
ACKNOWLEDGMENT
We would like to thank Dr. Kenneth L. Sutherland (Graduate School of Medicine, Hokkaido University, Sapporo, Japan) who kindly spared time for the English proofreading of the manuscript.
