Tenth Warren K. Sinclair Keynote Address?The Fukushima Nuclear Power Plant Accident and Comprehensive Health Risk Management

Just two years have passed since the Tokyo Electric Power Company-Fukushima Daiichi Nuclear Power Plant (NPP) accident, a multidimensional disaster that combined to destroy the local infrastructure on which the safety system depended and gave a serious impact to the world. Countermeasures including evacuation, sheltering, and control of the food chain were implemented in a timely manner by the Japanese government. However, there is a clear need for improvement, especially in the areas of nuclear safety and protection and also in the management of the radiation health risk during and even after the accident. To date there have been no acute radiation injuries. The radiation-related physical health consequences to the general public, including evacuees, are likely to be much lower than those arising from the Chernobyl nuclear reactor accident, because the radiation fallout and the subsequent environmental contamination were much more limited. However, the social, psychological, and economic impacts of the Fukushima NPP accident are expected to be considerable. Currently, continued monitoring and characterization of the levels of radioactivity in the environment and foods in Fukushima are vital for obtaining informed consent to the decisions on living in the areas already radiocontaminated and returning back to the evacuated areas once re-entry is permitted; it is also important to perform a realistic assessment of the radiation doses on the basis of measurements. We are currently implementing the official plans of the Fukushima Health Management Survey, which includes a basic survey for the estimation of the external doses that were received during the first 4 mo after the accident and four more detailed surveys (thyroid ultrasound examination, comprehensive health check-up, mental health and life-style survey, and survey of pregnant women and nursing mothers), with the aim to take care of the health of all of the residents of the Fukushima Prefecture for a long time

Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to ionizing radiation

Background: Proteins involved in the DNA damage response accumulate as microscopically-visible nuclear foci on the chromatin flanking DNA double-strand breaks (DSBs). As growth of ionizing radiation (IR)-induced foci amplifies the ATM-dependent DNA damage signal, the formation of discrete foci plays a crucial role in cell cycle checkpoint activation, especially in cells exposed to lower doses of IR. However, there is no quantitative parameter for the foci which considers both the number and their size. Therefore, we have developed a novel parameter for DNA damage signal based on the image analysis of the foci and quantified the amount of the signal sufficient for G2 arrest.Results: The parameter that we have developed here was designated as SOID. SOID is an abbreviation of Sum Of Integrated Density, which represents the sum of fluorescence of each focus within one nucleus. The SOID was calculated for individual nucleus as the sum of (area (total pixel numbers) of each focus) x (mean fluorescence intensity per pixel of each focus). Therefore, the SOID accounts for the number, size, and fluorescence density of IR-induced foci, and the parameter reflects the flux of DNA damage signal much more accurately than foci number. Using very low doses of X-rays, we performed a "two-way" comparison of SOID of Ser139-phosphorylated histone H2AX foci between G2-arrested cells and mitosis-progressing cells, and between mitosis-progressing cells in the presence or absence of ATM or Chk1/2 inhibitor, both of which abrogate IR-induced G2/M checkpoint. The analysis revealed that there was a threshold of DNA damage signal for G2 arrest, which was around 4000~5000 SOID. G2 cells with < 4000 SOID were neglected by G2/M checkpoint, and thus, the cells could progress to mitosis. Chromosome analysis revealed that the checkpoint-neglected and mitosis-progressing cells had approximately two chromatid breaks on average, indicating that 4000~5000 SOID was equivalent to a few DNA double strand breaks.Conclusions: We developed a novel parameter for quantitative analysis of DNA damage signal, and we determined the threshold of DNA damage signal for IR-induced G2 arrest, which was represented by 4000~5000 SOID. The present study emphasizes that not only the foci number but also the size of the foci must be taken into consideration for the proper quantification of DNA damage signal

Post-crisis efforts towards recovery and resilience after the Fukushima Daiichi Nuclear Power Plant accident

One of thewell-known radiation-associated late-onset cancers is childhood thyroid cancer as demonstrated around Chernobyl apparently from 1991. Therefore, immediately after the Fukushima Daiichi Nuclear Power Plant accident on March 2011, iodine thyroid blocking was considered regardless of its successful implementation or not at the indicated timing and places as one of the radiation protection measurements, in addition to evacuation and indoor sheltering, because a short-lived radioactive iodine was massively released into the environment which might crucially affect thyroid glands through inhalation and unrestricted consumption of contaminated food and milk. However, very fortunately, it is now increasingly believed that the exposure doses on the thyroid as well as whole body are too low to detect any radiation-associated cancer risk in Fukushima. Although the risk of radiation-associated health consequences of residents in Fukushima is quite different from that of Chernobyl and is considerably low based on the estimated radiation doses received during the accident for individuals, a large number of people have received psychosocial and mental stresses aggravated by radiation fear and anxiety, and remained in indeterminate and uncertain situation having been evacuated but not relocated. It is, therefore, critically important that best activities and practices related to recovery and resilience should be encouraged, supported and implemented at local and regional levels. Since psychosocial well-being of individuals and communities is the core element of resilience, local individuals, health professionals and authorities are uniquely positioned to identify and provide insight into what would provide the best resolution for their specific needs

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years

Biological Significance of DNA Damage Checkpoint and the Mode of Checkpoint Signal Amplification

It is generally accepted that DNA damage checkpoint is the mechanism that allows time for DNA damage repair. However, several lines of evidence challenge this paradigm, especially, in the case of G1 checkpoint. The first evidence is the complete difference between the repair kinetics of DNA double-strand breaks (very rapid) and the timing of G1 checkpoint induction (very slow) after ionizing radiation. The second evidence is that inactivation of p53, which is a central player of G1 checkpoint, does not render cells radiosensitive, rather, such cells become radioresistant. Moreover, it was shown that G1 arrest persists almost permanently after irradiation, until the time when most of the initial damage should be repaired and disappear. Therefore, cells should have a mechanism to maintain G1 checkpoint signaling by amplifying the signal from a limited number of damage. In this review, we discuss what is the bona fide role of G1 arrest and how G1 checkpoint signal is maintained long after irradiation

A Possible Role of Stress-Induced Premature Senescence, SIPS, as a Producer of the Stress-Resistant Microenvironment

The microenvironment is consisted both of soluble factors involving growth factors and of insoluble factors. Stroma cells contribute to form the microenvironment through a secretion of these factors. Fibroblast, which is known as stroma cells, also secretes various soluble/ insoluble factors, but the secretion level is significantly up-regulated when they reach to a finite replicative lifespan. Recent accumulating studies not only in vitro but also in vivo provide us that secreted proteins from senescent cells promote pro-survival pathway in bystander cells, especially tumor cells rather than normal cells. Since various stresses including ionizing radiation (IR) prematurely induces cellular senescent stage, called Stress-Induced Premature Senescence (SIPS), there is the possibility that the secretion pathway in cells undergoing SIPS is also activated. Here, we propose that pro-survival factor is secreted from SIPS cells to provide the stress-resistant microenvironment