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Klotho is an anti-aging, single-pass transmembrane protein found mainly in the kidney. Although aging is likely to be associated with DNA damage, the involvement of Klotho in protecting cells from DNA damage is still unclear. In this study, we examined DNA damage in human kidney cells and mouse kidney tissue after ionizing radiation (IR). The depletion and overexpression of Klotho in human kidney cells reduced and increased the cell survival rates after IR, respectively. The formation of γ-H2AX foci, representing DNA damage, was significantly elevated immediately after IR in cells with Klotho depletion and decreased in cells overexpressing Klotho. These results were confirmed in mouse renal tissues after IR. Quantification of DNA damage by a comet assay revealed that the Klotho knockdown significantly increased the amount of DNA damage immediately after IR, suggesting that Klotho protects chromosomal DNA from the induction of damage, rather than facilitating DNA repair. Consistent with this notion, Klotho was detected in both the nucleus and cytoplasm. In the nucleus, Klotho may serve to protect chromosomal DNA from damage, leading to its anti-aging effects.

Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Furthermore, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared with age-matched nonsmokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared with the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis.

The International Atomic Energy Agency (IAEA) and Hiroshima International Council for Health Care of the Radiation-Exposed (HICARE) jointly organized two relevant workshops in Hiroshima, Japan, i.e. a Training Meeting ‘Biodosimetry in the 21st century’ (BIODOSE-21) on 10–14 June 2013 and a Workshop on ‘Biological and internal dosimetry: recent advance and clinical applications’ which took place between 17 and 21 February 2020. The main objective of the first meeting was to develop the ability of biodosimetry laboratories to use mature and novel techniques in biological dosimetry for the estimation of radiation doses received by individuals and populations. This meeting had a special focus on the Asia-Pacific region and was connected with the then on-going IAEA Coordinated Research Project (CRP) E35008 ‘Strengthening of “Biological dosimetry” in IAEA Member States: Improvement of current techniques and intensification of collaboration and networking among the different institutes’ (2012–17). The meeting was attended by 25 participants, which included 11 lecturers. The 14 trainees for this meeting came from India, Indonesia, Japan, Malaysia, Philippines, Republic of Korea, Singapore, Thailand and Vietnam. During the meeting 13 lectures by HICARE and IAEA invited lecturers were delivered besides eight research reports presented by the IAEA CRP E35008 network centers from the Asia-Pacific region. Two laboratory exercises were also undertaken, one each at Hiroshima University and the Radiation Effects Research Foundation (RERF). The second training workshop aimed to discuss with the participants the use of mature and novel techniques in biological and internal dosimetry for the estimation of radiation effects by accidental, environmental and medical exposures. The workshop was attended by 19 participants from Indonesia, Jordan, Oman, Philippines, Singapore, Syrian Arab Republic, Thailand, UAE, USA and Yemen. The main outcome of both meetings was a review of the state-of-the-art of biodosimetry and internal dosimetry and their future perspectives in medical management. This report highlights the learning outcome of two meetings for the benefit of all stake-holders in the field of biological and internal dosimetry.

ObjectivesThis study aimed to identify factors that delayed emergency medical services (EMS) in evacuation order zones after the 2011 Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident and to investigate how the lifting of the evacuation affected these factors over time.DesignThis research was a retrospective observational study. The primary outcome measure was onsite EMS time. A gradient boosting model and a decision tree were used to find the boundary values for factors that reduce EMS.SettingThe target area was Minamisoma City, Fukushima, Japan that was partly designated as an evacuation order zone after the 2011 Fukushima disaster, which was lifted due to decreased radiation.ParticipantsThis study included patients transferred by EMS from 1 January 2013 through 31 October 2018. Patients who were not transported and those transported for community events, interhospital patient transfer and natural disasters were excluded.Outcome measuresThis study evaluated the total EMS time using on-site time which is the time from arrival at the scene to departure to the destination, and other independent factors.ResultsThe total number of transports was 12 043. The decision tree revealed that the major factors that prolonged onsite time were time of day and latitude, except for differences by year. While latitude was a major factor in extending on-site time until 2016, the effect of latitude decreased and that of time of day became more significant since 2017. The boundary was located at N37.695° latitude.ConclusionsThe onsite time delay in EMS in evacuation order zones is largely due to regional factors from north to south and the time of day. However, the north-south regional factor decreased with the lifting of evacuation orders.

Contrast media has been shown to induce nephropathy (i.e., contrast-induced nephropathy) after various types of radiological examinations. The molecular mechanism of contrast-induced nephropathy has been unclear. In this study, we investigated the mechanism of contrast-induced nephropathy by examining the effects of combined treatment of contrast medium and ionizing radiation on kidney cells in vitro and kidney tissue in vivo. In human renal tubular epithelium cells, immunofluorescence analysis revealed that iohexol increased the numbers of radiation-induced γH2AX nuclear foci. The numbers of γH2AX nuclear foci remained high at 24 h, suggesting that some radiation-induced double-strand breaks remain unrepaired in the presence of iohexol. We established a mouse model of contrast-induced nephropathy, then showed that iohexol and ionizing radiation synergistically reduced renal function and induced double-strand breaks. Importantly, iohexol induced significant macrophage accumulation and oxidative DNA damage in the kidneys of contrast-induced nephropathy model mice in the absence of ionizing radiation; these effects were amplified by ionizing radiation. The results suggest that underlying inflammation and oxidative DNA damage caused by iohexol contribute to the enhancement of radiation-induced double-strand breaks, leading to contrast-induced nephropathy.