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S1. The percentage of TIG-3 and MRC-5 cells with alpha-SMA staining exposed to indicated doses is shown in the graph. S2. Tumor volumes of HeLa, HeLa+MRC-5 0FR tumors, HeLa+MRC-5 0.05FR tumors, HeLa+MRC-5 NAC 0FR tumors, and HeLa+MRC-5 0.05FR tumors.

Fibroblasts are a key stromal cell in the tumor microenvironment (TME) and promote tumor growth via release of various growth factors. Stromal fibroblasts in cancer, called cancer-associated fibroblasts (CAF), are related to myofibroblasts, an activated form of fibroblast. While investigating the role of stroma fibroblasts on radiation-related carcinogenesis, it was observed following long-term fractionated radiation (FR) that the morphology of human diploid fibroblasts changed from smaller spindle shapes to larger flat shapes. These cells expressed smooth muscle actin (α-SMA) and platelet-derived growth factor receptors, markers of myofibroblasts and CAFs, respectively. Long-term FR induces progressive damage to the fibroblast nucleus and mitochondria via increases in mitochondrial reactive oxygen species (ROS) levels. Here, it is demonstrated that long-term FR-induced α-SMA–positive cells have decreased mitochondrial membrane potential and activated oxidative stress responses. Antioxidant N-acetyl cysteine suppressed radiation-induced mitochondrial damage and generation of myofibroblasts. These results indicate that mitochondrial ROS are associated with the acquisition of myofibroblasts after long-term FR. Mechanistically, mitochondrial ROS activated TGFβ signaling which in turn mediated the expression of α-SMA in radiation-induced myofibroblasts. Finally, in vivo tumor growth analysis in a human tumor xenograft model system revealed that long-term FR-induced myofibroblasts promote tumor growth by enhancing angiogenesis.Implications: Radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts such as activation of TGFβ and angiogenic signaling pathways. Mol Cancer Res; 16(11); 1676–86. ©2018 AACR.

Induction of alpha-SMA after acute single radiation

Background: The present study investigated the radiation dose distribution of balloon kyphoplasty (BKP) among surgeons and medical staff, and this is the first research to observe such exposure in Japan.Materials and Methods: The study subjects were an orthopedic surgeon (n = 1) and surgical staff (n = 9) who intervened in BKP surgery performed at the National Hospital Organization Disaster Medical Center (Tokyo, Japan) between March 2019 and October 2019. Only disposable protective gloves (0.022 mmPb equivalent thickness or less) and trunk protectors were used, and no protective glasses or thyroid drapes were used.Results and Discussion: The surgery time per vertebral body was 36.2 minutes, and the fluoroscopic time was 6.8 minutes. The average exposure dose per vertebral body was 1.46 mSv for the finger (70 μm dose equivalent), 0.24 mSv for the lens of the eye (3 mm dose equivalent), 0.11 mSv for the neck (10 mm dose equivalent), and 0.03 mSv for the chest (10 mm dose equivalent) under the protective suit.The estimated cumulative radiation exposure dose of 23 cases of BKP was calculated to be 50.37 mSv for the fingers, 8.27 mSv for the lens, 3.91 mSv for the neck, and 1.15 mSv for the chest.Conclusion: It is important to know the exposure dose of orthopedic surgeons, implement measures for exposure reduction, and verify the safety of daily use of radiation during surgery and examination.

Background: For proper monitoring of the eye lens dose, an appropriate calibration factor of a dosimeter and information about the mean energies of X-rays are indispensable. The scattered X-ray energy spectra should be well characterized in medical practices where eye lenses of medical staffs might be high.Materials and Methods: Scattered X-ray energy spectra were experimentally derived for three different types of X-ray diagnostic and therapeutic equipment, i.e., the computed tomography (CT) scan, the angiography and the fluoroscopy. A commercially available CdZnTe (CZT) spectrometer with a lead collimator was employed for the measurement of scattered X-rays, which was performed in the usual manner.Results and Discussion: From the obtained energy spectra, the mean energies of the scattered X-rays lied between 40 and 60 keV. This also agreed with that obtained by the conventional half value layer method.Conclusion: The scattered X-rays to which medical workers may be exposed in the region around the eyes were characterized by means of spectrometry. The obtained mean energies of the scattered X-rays were found to match the flat region of the dosimeter response.

Background: In Japan, new regulations that revise the dose limit for the lens of the eye (hereafter the lens), operational quantities, and measurement positions for the lens dose were enforced in April 2021. Based on the international safety standards, national guidelines, the results of the Radiation Safety Research Promotion Fund of the Nuclear Regulation Authority, and other studies, the Working Group of Radiation Protection Standardization Committee, the Japan Health Physics Society (JHPS) developed a guideline for radiation dose monitoring for the lens.Materials and Methods: The Working Group of the JHPS discussed the criteria of non-uniform exposure and the management criteria set not to exceed the dose limit for the lens.Results and Discussion: In July 2020, the JHPS guideline was published. The guideline consists of three parts: main text, explanations, and 26 examples. In the questions, the corresponding answers were prepared, and specific examples were provided to enable similar cases to be addressed.Conclusion: With the development of the guideline on radiation dose monitoring of the lens, radiation managers and workers will be able to smoothly comply with revised regulations and optimize radiation protection.

Ionizing radiation exposure affects the redox state in vivo. Recently, whole-blood antioxidant capacity (WBAC) has been reported to decrease in a dose-dependent manner after acute total body irradiation (TBI). However, changes in WBAC after localized and chronic irradiations have not been reported. This study analyzed changes to WBAC in mice after either localized irradiation (irradiation of the left hind leg only) or chronic TBI using the i-STrap method. Leg-localized irradiation exerted limited effects on WBAC, while WBAC decreased in a dose rate-dependent manner after TBI. Further, the WBAC reached the minimum value in a shorter period at a smaller dose rate. Our results suggest that changes in WBAC do not directly reflect absorbed dose, but may reflect radiation-induced biological damage at the systemic level. This study will contribute to the understanding of radiation-induced injuries and diseases, and will facilitate the establishment of biomarkers for radiation exposure.

Ionizing radiation exposure affects the redox state in vivo. Recently, whole-blood antioxidant capacity (WBAC) has been reported to decrease in a dose-dependent manner after acute total body irradiation (TBI). However, changes in WBAC after localized and chronic irradiations have not been reported. This study analyzed changes to WBAC in mice after either localized irradiation (irradiation of the left hind leg only) or chronic TBI using the i-STrap method. Leg-localized irradiation exerted limited effects on WBAC, while WBAC decreased in a dose rate-dependent manner after TBI. Further, the WBAC reached the minimum value in a shorter period at a smaller dose rate. Our results suggest that changes in WBAC do not directly reflect absorbed dose, but may reflect radiation-induced biological damage at the systemic level. This study will contribute to the understanding of radiation-induced injuries and diseases, and will facilitate the establishment of biomarkers for radiation exposure.

Few studies have investigated personal exposure concentrations of not only some volatile organic compounds but also more types of chemicals including acidic gases and acrolein. We measured the personal exposure concentrations of 35 chemicals including these chemicals in indoor and outdoor air in Chiba-shi, Japan, for 7 days in summer and winter to assess the associated health risks in 22 people. The personal exposure concentrations of nitrogen dioxide were higher in winter than in summer, and those of formaldehyde, p-dichlorobenzene, and tetradecane were higher in summer than in winter. The personal exposure concentrations were mostly equal to or lower than the concentrations in indoor air, contrary to the results of a lot of previous studies. The high-risk chemicals based on personal exposure concentrations were identified as acrolein (max. 0.43 μg/m3), benzene (max. 3.1 μg/m3), and hexane (max. 220 μg/m3) in summer, and acrolein (max. 0.31 μg/m3), nitrogen dioxide (max. 320 μg/m3), benzene (max. 5.2 μg/m3), formic acid (max. 70 μg/m3), and hexane (max. 290 μg/m3) in winter. In addition, we estimated personal exposure concentrations according to the time spent at home and the chemical concentrations in indoor and outdoor air. We found that the estimated concentrations of some participants largely differed from the measured ones indicating that it is difficult to estimate personal exposure concentrations based on only these data.

Interventional radiology (IR) physicians must be equipped with personal passive dosimeters and personal protective equipment (PPE); however, they are inconsistently used. Therefore, we aimed to explore practical measures to increase PPE usage and ascertain whether these measures could lead to an actual decrease in exposure doses to IR physicians. Dosimeters and PPE were visually inspected. Then, a pre-operative briefing was conducted as a direct intervention, and the use of dosimeters and PPE was verbally confirmed. Finally, the intervention effect was verified by measuring the use rates and individual exposure doses. Because of the intervention, the use rate markedly improved and was almost 100%. However, both the effective dose rate (effective dose/fluoroscopy time) and the lens equivalent dose rate (lens equivalent dose/fluoroscopy time) showed that the intervention led to a statistically significant increase in exposure (effective dose rate: p = 0.033; lens equivalent dose rate: p = 0.003). In conclusion, the proper use of dosimeters and PPE raised the radiation exposure values for IR physicians immediately after the intervention, which was hypothesized to be due to the inclusion of exposure overlooked to date and the changes in the dosimeter management method from a single- to a double-dosimeter approach.

In April 2011, the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens. Such a new occupational lens dose limit has thus far been implemented in many countries, and there are extensive discussions toward its regulatory implementation in other countries. In Japan, discussions in the Japan Health Physics Society (JHPS) began in April 2013 and in Radiation Council in July 2017, and the new occupational lens dose limit was implemented into regulation in April 2021. To share our experience, we have published a series of papers summarizing situations in Japan: the first paper based on information available by early 2017, and the second paper by early 2019. This paper (our third paper of this series) aims to review updated information available by mid-2022, such as regarding regulatory implementation of the new occupational lens dose limit, recent discussions by relevant ministries based on the opinion from the council, establishment process of safety and health management systems, the JHPS guidelines on lens dose monitoring and radiation safety, voluntary countermeasures of the licensees, development of lens dose calibration method, and recent studies on exposure of the lens in nuclear workers and biological effect on the lens.

Heated tobacco products (HTPs) have become increasingly popular among smokers, especially among young adults in Japan in recent years. Assessments of secondhand tobacco smoke (SHS) exposure due to HTPs are scarce. The present study aimed to assess the urinary levels of total nicotine metabolites (TNMs) of non-smoking spouses and their children following SHS exposure due to their fathers’ use of HTPs. A total of 41 families including 129 participants were recruited between 2018 and 2021. The number of non-smoking spouses and children of the fathers who smoke combustion cigarettes, the fathers who use HTPs, and the fathers who are non-users or have never smoked was 27, 66, and 36, respectively. The urinary levels of TNMs, including cotinine (Cot) and 3′-hydroxycotinine (3-OHCot), were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The spouses and children of fathers who use HTPs had significantly higher levels of TNMs in their urine compared to those with fathers who were non-smokers or non-users. The current study is the first to assess SHS exposure due to HTP use, and to suggest the importance of strategies to prevent exposure to SHS from HTP use in public places and educational strategies to protect non-smokers from secondhand HTP aerosol exposure in households and other private places.

Objective In contrast to the association between excess weight and sickness absence (SA), the association in relation to underweight has been under‐researched. This study aimed to examine the effects of BMI at both extremes of its distribution on SA. Methods Data came from the Japan Epidemiology Collaboration on Occupational Health study of 77,760 workers aged 20 to 59 years (66,166 males, 11,594 females). Information was collected on medically certified long‐term SA (LTSA) (i.e., SA lasting ≥ 30 consecutive days) from April 2012 to March 2017. A sex‐specific Cox proportional hazards model was used to investigate the associations. Results Among males, both obesity (hazard ratio [HR] = 1.81, 95% CI: 1.50‐2.17) and underweight (HR = 1.56, 95% CI: 1.23‐1.96) were significantly associated with LTSA compared with normal weight. This U‐shaped association between BMI categories and LTSA was observed both for mental and physical disorders. Among females, an elevated risk was observed among those with overweight (HR = 1.54, 95% CI: 1.16‐2.05). Conclusions In a cohort of the Japanese working‐age population, both obesity and underweight were associated with a greater risk of LTSA in males. Future research should not overlook the excess risk of LTSA associated with underweight.

The purpose of this study was to evaluate the effectiveness of organ effect modulation (OEM) in reducing the lens dose in 4D computed tomography (CT) of the head in volume-acquisition (NVA) mode. Six radiophotoluminescent dosemeters were placed on the head of a RANDO phantom. The doses absorbed by the organs and image noise change rate were determined. The lens doses without OEM (i.e. in the OEMoff case) were higher than those with the same target standard deviation and volume-computed tomography dose index (CTDIvol) as in the OEMoff case (p

Purpose We investigated occupational dose to the lens of the eye for physicians engaged in radiology procedures. We evaluated the potential for compliance with the new‐equivalent dose limits to the lens of the eye. Further, a “multiple radiation protection” protocol was proposed according to the basic principles of occupational health, and its effectiveness was estimated. Methods Physicians engaged in radiology procedure at medical facilities in Japan were included in this study. The eye lens dose (3‐mm dose equivalent: Hp(3)) for each participant was measured using a small radio‐photoluminescence glass dosimeter mounted on lead glasses. Physicians were directed to procedure multiple radiation protection measures to evaluate their usefulness. Results The Hp(3) was reduced by multiple radiation protection in all physicians. In particular, the Hp(3) reduced from 207.7 to 43.2 μSv/procedure and from 21.6 to 10.2 μSv/procedure in cardiovascular internal physician and cerebrovascular physician, respectively, after the implementation of the proposed multiple radiation protection measures. The dose reduction rate of these measures was 53% (range: 37%–79%). Conclusions The radiation doses received by the eye lenses of physicians engaged in radiology procedure may exceed the dose limits to the lens of the eye if radio‐protective equipment and imaging conditions are not properly controlled. However, based on the lens equivalent dose data, the implementation of “multiple radiation protection” according to the basic principles of occupational health can ensure compliance with the new‐equivalent dose limits to the lens of the eye without placing an undue burden on individual physicians or medical facilities.

Indoor air quality (IAQ) can greatly affect health in people spending much time indoors. However, the influence of IAQ on personal exposure to chemical compounds in Japan remains poorly investigated. Hence, this study aimed to clarify this influence thoroughly within one apartment. We surveyed the concentrations of 61 chemical compounds in the air in nine different spaces within an apartment unit, as well as the personal exposure of two residents in Japan. Using three kinds of diffusive samplers, this study was conducted continuously for 7 days in summer and winter. Health risks were evaluated by calculating the margin of exposure (MOE) using the measured concentrations. Some chemical concentrations showed large spatial variations and the personal exposure concentrations of these compounds also differed among residents. According to the calculated MOE, the chemicals with the highest health risk were acrolein, p-dichlorobenzene, and acetaldehyde in summer and acrolein, nitrogen dioxide, formic acid, p-dichlorobenzene, and benzene in winter. The IAQ of the house could be divided in two, and the IAQ in the space where residents spent much time (i.e., bedroom) highly affected each of the residents’ exposure. Investigating chemical concentrations in multiple spaces (including bedroom and living room) is necessary to understand the effect of IAQ on personal exposure.

A short curtain that improves on the low versatility of existing long curtains was developed as a dedicated radiation protective device for the over-table tube fluorographic imaging units. The effect of this short curtain in preventing cataracts was then examined. First, the physician lens dose reduction rate was obtained at the position of the lens. Next, the reduction rate in the collective equivalent dose for the lens of the physician’s eye was estimated. The results showed that lens dose reduction rates with the long curtain and the short curtain were 88.9% (literature-based value) and 17.6%, respectively, higher with the long curtain. In our hospital, the reduction rate in the collective equivalent dose for the lens of the physician’s eye was 9.8% and 17.6% with a procedures mixture, using the long curtain where technically possible and no curtain in all other procedures, and the short curtain in all procedures, respectively, higher with the short curtain. Moreover, a best available for curtains raised the reduction rate in the collective equivalent dose for the lens of the physician’s eye a maximum of 25.5%. By introducing the short curtain, it can be expected to have an effect in preventing cataracts in medical staff.

Objective The Japanese chemical intolerance (JCI) study was conducted in January 2012 with a cohort of 7245 adults from population-based sampling. This study aimed to investigate the childhood constitutional and environmental factors involved in the development of chronic CI from the prospective cohort study. Methods In the cohort, 4683 persons were identified after six years. Self-reported questionnaires were administered to the subjects to obtain information on CI status; medical history; constitution, lifestyle, and housing environment during childhood; and recent psychosomatic states. We assessed the differences between individuals with persisting CI status during the follow-up (defined as chronic CI) and controls not having CI status during the follow-up. Results A total of 2500 individuals responded. Multiple logistic regression analyses revealed significant associations between chronic CI and motion sickness to car or bus and allergic conjunctivitis during childhood. Significant associations between a possible increased risk of CI and the existence of high-voltage power lines close to housing, the use of vinyl covering in wall material, the use of strong perfume by a family member, and the experience of stinky odor of paint or wax at elementary school were observed. However, the use of carpet in floor material and plaster coating in wall material was associated with a possible decreased risk of CI. Conclusions Some potential constitutional predisposition from childhood, including inherent susceptibility in the autonomic nervous system may be involved in the development of CI.

Background Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan. Methods We followed 70 896 workers aged 20–59 years (60 133 males, 10 763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (ie, SL lasting ≥30 consecutive days). Cause-specific analyses were also conducted. Results A total of 1777 people took long-term SL during a follow-up of 307 749 person years. Compared with never-smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.32; 95% confidence interval [CI] = 1.19 to 1.48). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.44, 95% CI = 1.22 to 1.69), cancer (HR = 1.49, 95% CI = 1.10 to 2.01), cardiovascular disease (CVD; HR = 2.16, 95% CI = 1.31 to 3.55), and injuries/external causes (HR = 1.83, 95% CI = 1.31 to 2.58). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.38, 95% CI = 0.99 to 1.92). Low-intensity smoking (ie, 1–10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to injuries/external causes compared with never-smokers. Conclusion In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term SL. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan. Implications Our study contributes to the literature on the association between smoking and SL in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on SL given that there is growing evidence of an elevated health risk associated with low-intensity smoking.

In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval [CI]: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.

Accidental radiation exposure that is due to a nuclear accident or terrorism using radioactive materials has severe detrimental effects on human health, and it can manifest as acute radiation syndrome depending on the dose and distribution of the radiation. Therefore, the development of radiation countermeasure agents is urgently needed to protect humans against radiation injury. Besides nuclear DNA, the mitochondria are important targets of ionizing radiation (IR) because these organelles generate reactive oxygen species (ROS). Recently, we revealed that mitochondrial ROS-activated cell signaling is associated with IR-induced tumor formation. Here, we investigated the effectiveness of ascorbic acid and epicatechin (EC) in scavenging ROS as radiation countermeasure agents by using human cells and mouse. Preradiation and postradiation treatments with EC mitigate ROS-mediated mitochondrial damage, IR-induced oxidative stress responses including reduction of superoxide dismutase activity, and elevated nuclear factor erythroid 2-related factor 2 expression, and they improve human fibroblast survival. As well as in vitro, EC mitigated ROS-mediated mitochondrial damage after exposure to IR in vivo in mouse platelets. Furthermore, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo. In summary, EC is a potentially viable countermeasure agent that is immediately effective against accidental IR exposure by targeting mitochondria-mediated oxidative stress.-Shimura, T., Koyama, M., Aono, D., Kunugita, N. Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells.

Air pollution related problems in urban areas of developing countries get bigger quickly. Yangon is the most urbanized and most densely populated city in Myanmar. Information on air quality of Yangon is still lacking. Therefore, we conducted this study for initial assessment of outdoor and indoor air quality of Yangon. Four kinds of diffusive air samplers were used to measure volatile organic compounds (VOCs), ozone and carbonyl compounds, acidic gases and ammonia. As a result of this study, higher alkanes were found dominant among outdoor VOCs. Benzene/toluene ratios ranged from 0.15 to 0.53. Formaldehyde/acetaldehyde ratios varied from 1.5 to 2.4. Maximum outdoor ozone value was 26 μgm−3. A strong negative correlation between outdoor ozone and nitrogen dioxide concentrations was noted. Compared with previous local studies, outdoor nitrogen dioxide and sulfur dioxide concentrations were found to be on the increasing trend. The indoor/outdoor ratios at some sites revealed that there were indoor sources for α-pinene, d-limonene, p-dichlorobenzene and methyl isobutyl ketone. The ratios of pollutants with outdoor sources mostly ranged between 1 and 2. In conclusions, although it is a preliminary assessment, the findings can provide invaluable information towards comprehensive picture of air quality of Yangon. Outdoor air quality is found contaminated with pollutants most of which are traffic-related indicating that the city is now facing high traffic volume greater than before. Indoor air quality is varied with indoor characteristics of the buildings. Gases with health concern are identified in indoor air. Inadequate ventilation may precipitate poor indoor air quality.