Improving radiation dosimetry with an automated micronucleus scoring system: correction of automated scoring errors.

Radiation dose estimations performed by automated counting of micronuclei (MN) have been studied for their utility for triage following large-scale radiological incidents; although speed is essential, it also is essential to estimate radiation doses as accurately as possible for long-term epidemiological follow-up. Our goal in this study was to evaluate and improve the performance of automated MN counting for biodosimetry using the cytokinesis-block micronucleus (CBMN) assay. We measured false detection rates and used them to improve the accuracy of dosimetry. The average false-positive rate for binucleated cells was 1.14%; average false-positive and -negative MN rates were 1.03% and 3.50%, respectively. Detection errors seemed to be correlated with radiation dose. Correction of errors by visual inspection of images used for automated counting, called the semi-automated and manual scoring method, increased accuracy of dose estimation. Our findings suggest that dose assessment of the automated MN scoring system can be improved by subsequent error correction, which could be useful for performing biodosimetry on large numbers of people rapidly, accurately, and efficiently.

Reliability and Validity of a Nationwide Survey (the Korean Radiation Workers Study).

BACKGROUND: This study aimed to evaluate the reliability and validity of the self-administered questionnaire for Korean radiation workers. METHODS: From May 24, 2016, to June 30, 2017, 20,608 participants completed the questionnaire, providing information on sociodemographics, lifestyle, work history and practices, medical radiation exposure, and medical history, which was linked to the National Dose Registry and the National Cancer Registry. The validity of the questionnaire was evaluated using the responses of 20,608 workers, and reliability was evaluated using the responses of 3043 workers who responded to the survey twice. RESULTS: Responses concerning demographic characteristics and lifestyle showed reliability with a moderate-to-high agreement (kappa: 0.43-0.99), whereas responses concerning occupation and medical radiation exposure had a wide range of agreement (kappa: 0.05-0.95), possibly owing to temporal variability during employment. Regarding validity, responses to the question about the first year of employment had an excellent agreement with the national registry (intraclass correlation coefficient = 0.9); however, responses on cancer history had a wide range of agreement (kappa: 0.22-0.85). CONCLUSION: Although the reliability and validity of the questionnaire were not distinguished by demographic characteristics, they tended to be low among participants whose occupational radiation exposure was minimal. Overall, the information collected can be reliable for epidemiological studies; however, caution must be exercised when using information such as medical exposure and work practices, which are prone to temporal variability.

Non-cancer disease prevalence and association with occupational radiation exposure among Korean radiation workers.

Radiation-induced cancer risks have known stochastic effects; however, regarding non-cancer diseases, evidence of risk at low radiation doses remains unclear. We aimed to identify underlying characteristics concerning non-cancer disease prevalence and determine associations with radiation dose among Korean radiation workers. Using a nationwide baseline survey, 20,608 workers were enrolled. Data concerning participant demographics, occupational characteristics, lifestyle, and lifetime prevalence of non-cancer diseases were linked to a national dose registry. We compared non-cancer disease prevalences in the Korean general population with those in this cohort and undertook a dose-response analysis concerning the cumulative dose. Hyperlipidemia (10.6%), circulatory (9.6%), and respiratory (4.1%) system diseases, followed by thyroid diseases (3.5%), had the highest prevalences, with hyperlipidemia, thyroid diseases, and hepatitis prevalence being higher in the cohort than in the general population. Radiation doses were associated with elevated prevalences of most diseases; however, associations were attenuated and not significant after adjusting for confounders, except for musculoskeletal system diseases (prevalence odds ratio [POR]/10 mSv, 1.03; 95% confidence interval [CI] 1.00-1.07) and cataracts (POR/10 mSv, 1.04; 95% CI 1.00-1.07). Further studies are warranted to investigate the causality of those non-cancer diseases involving more varied confounders such as physical and psychosocial stresses and ultraviolet light.

Estimation of the historical radiation dose of Korean radiation workers, 1961-1983.

Accurate dosimetry plays a key role in evaluating the radiation-induced health risks of radiation workers. The National Dose Registry in Korea contains the dose records of radiation workers in nuclear-related occupations since 1984. Thus, radiation doses for workers before 1984 are often sparse or missing. This study aimed to estimate the historical radiation dose before 1984 for radiation workers in Korea based on dose reconstruction models. The dose reconstruction models were derived from the nationwide self-administered questionnaire survey and the personal badge doses for workers in the cohort of the Korean Radiation Worker Study. The mean estimated annual doses between 1984 and 2016 from the dose reconstruction model were 4.67-0.6 mSv, which closely matched the reported doses of 4.51-0.43 mSv. The mean estimated annual doses between 1961 and 1983 based on the exposure scenarios developed by factors associated with radiation doses ranged from 11.08 to 4.82 mSv. The mean estimated annual doses of individuals in the cohort from 1961 to 1983 ranged from 11.15 to 4.88 mSv. Although caution needs to be exercised in the interpretation of these estimations due to uncertainty owed to the nature of extrapolation beyond the range of observed data, this study offers a sense of the radiation doses for workers during Korea's early period of radiation-related activities, which can be a useful piece of information for radiation-induced health risk assessments.

Assessment of an Emergency Medicine System for Radiation Accidents in Korea: A State Survey of the Workers Involved the Medical Response to Radiation Accidents.

Radiation emergency medicine systems are operated around the world to provide special care for the injured that require immediate medical attention in accidents. The objective of this survey was to evaluate people's perception of those who design the emergency medical plan for radiation accidents and those who supervise it in Korea. A questionnaire survey was conducted on the people involved in a regulatory system for medical response in a radiation emergency. Of 150 survey recipients, 133 (88.7%) completed the survey, including 92 workers and 41 inspectors. The respondents expressed the view that the national emergency medical plan is prepared above the average level using a Likert-style scale of 1 to 5 (mean = 3.55, SD = 0.74). Interestingly, using the Mann-Whitney U test, it could be shown that inspectors evaluated the emergency medical system for radiation accidents more strictly in all of the questions than the licensee workers, especially on radiation medical emergency preparedness (p = 0.004) and the governmental regulatory policy for radiation safety (p = 0.007). For a more efficient system of radiation emergency medicine, licensee workers prioritized the workforce, whereas inspectors favored laws and regulations for safety. The survey results show different perspectives between inspectors and licensee workers, which stem from the actual properties of each occupational role in the regulatory system for radiation medical emergency. These data could be utilized for communication and interaction with relevant people to improve the medical response preparedness against radiation accidents.

Interventional radiologists have a higher rate of chromosomal damage due to occupational radiation exposure: a dicentric chromosome assay.

OBJECTIVES: There are growing concerns regarding radiation exposure in medical workers who perform interventional fluoroscopy procedures. Owing to the nature of certain interventional procedures, workers may be subjected to partial-body radiation exposure that is high enough to cause local damage. We aimed to investigate the level of radiation exposure in interventional radiologists in South Korea by performing cytogenetic biodosimetry, particularly focusing on partial-body exposure. METHODS: Interventional radiologists (n = 52) completed a questionnaire, providing information about their work history and practices. Blood samples were collected and processed for a dicentric chromosome assay. We determined Papworth's U-value to assess the conformity of dicentrics with the Poisson distribution to estimate the partial-body exposures of the radiologists. RESULTS: Radiologists had a higher number of dicentrics than the normal population and industrial radiographers. Indeed, subjects with a U-value of > 1.96, an indicator of heterogeneous exposure, were observed more frequently; 4.67 ± 0.81% of their body was irradiated at an average dose of 4.64 ± 0.67 Gy. Logistic regression analysis revealed that the total duration of all interventional procedures per week was associated with partial-body exposure levels. CONCLUSIONS: Our findings suggest that interventional radiologists had greater chromosomal damages than those in other occupational groups, and their partial-body exposure levels might be high enough to cause local damage. Use of special dosimeters to monitor partial-body exposure, as well as restricting the time and frequency of interventional procedures, could help reduce occupational radiation exposure. KEY POINTS: • Interventional radiologists had a higher number of dicentrics than the normal population and industrial radiographers. • The level of partial-body exposure of interventional radiologists might be high enough to cause occupational local damage such as a skin cancer in fingers. • Restricting the duration and frequency of interventional procedures might be helpful in reducing occupational radiation exposure.

Transfusion of γ-irradiated blood components to individuals does not compromise the cytogenetic dose assessment.

Most blood components for transfusions are irradiated ex vivo to prevent transfusion-associated graft-versus-host disease (TA-GvHD); this irradiation can potentially affect the cytogenetic dose assessment of patients showing acute radiation syndrome (ARS) with bone marrow suppression or acute anaemia. Whole blood samples from five donors were irradiated with 0, 10 or 25 Gy γ-rays. The mitotic activity of each cultured blood sample was measured by calculating the mitotic index. A dicentric chromosome assay was used to evaluate the chromosomal aberrations and absorbed dose of blood lymphocytes. Mitogenic activity and scorable metaphase spreads were significantly decreased in the blood samples irradiated with 10 and 25 Gy (p < 0.001). Moreover, a significant increase in the mean scores of all types of chromosomal aberrations in the 10 Gy γ-irradiated samples was observed, with the estimated dose being 11.3 Gy (95% CI: 10.67-11.95 Gy); however, we were unable to estimate the exposure dose in the 25 Gy γ-irradiated samples due to a limited number of scorable metaphase spreads. The mitotic index of the 25 Gy γ-irradiated whole blood samples was significantly suppressed by more than 4-log fold. Thus, in the present study, we evaluated the effects of recommended radiation doses in γ-irradiated transplantation blood components using cytogenetic dosimetry. These results suggest that the partial transfusion of blood components to patients with ARS or acute anaemia did not compromise the estimation of the exposure dose using cytogenetic dosimetry.

Increased Incidence of Thyroid Cancer in Occupational Radiation Epidemiology: Attribution to Screening among Radiation Workers.

In most studies on radiation workers, the incidence of thyroid cancer was determined to be higher than among the general population; this is generally assumed to be due to overdiagnosis through thyroid screening. However, there is a lack of evidence on the association between thyroid screening and increased thyroid cancer incidence in most occupational studies. In this study, we compared thyroid cancer screening rates between the general population and radiation workers with various occupations and examined the relationship between these rates and thyroid cancer incidence. We compared thyroid screening rates between radiation workers and the general population with age- and sex-standardized screening ratios (SSRs) using data from two national surveys conducted during 2015-2017 in Korea, and assessed the correlation between these ratios and age- and sex-standardized incidence ratios (SIRs) for thyroid cancer. Screening rates were higher among radiation workers than among the general population, with an overall SSR of 1.58 (95% confidence interval: 1.54-1.62). When various types of occupations were compared, those with an increased SSR also had an increased SIR. SSRs remained high even when the screening period was restricted to the year preceding the survey (the year after the establishment of guidelines for thyroid cancer screening aimed at reducing overdiagnosis). In conclusion, the increased incidence of thyroid cancer among radiation workers compared to that among the general population can be attributed mainly to increased thyroid screening rates. Additional efforts are needed to reduce unnecessary thyroid cancer screening in occupational populations, particularly in those with better access to healthcare, in terms of clinical rationale and for assessing the true increase in thyroid cancer incidence.

Korean-specific biokinetic model for iodine in radiological protection.

The International Commission on Radiological Protection (ICRP) recently adopted a detailed biokinetic model for systemic iodine with reference transfer coefficients based on typical worldwide dietary intakes of stable iodine. The regional data provided demonstrate that the ICRP reference thyroidal biokinetics may differ substantially across regions with atypically low or high dietary intakes of stable iodine. Importantly, the design of the ICRP model facilitates modifications of reference thyroidal kinetics based on regional dietary iodine intake. The present study extended the ICRP model to the South Korean population, whose dietary iodine intake is much higher than the global mean. The following three transfer coefficients were selected as targets for Korean-specific values: thyroidal uptake rate (λ1), hormonal secretion rate (λ4) and leakage rate of thyroidal organic iodine as inorganic iodide (λ5). The Korean-specific values forλ1,λ4andλ5were determined to be 4.48, 0.0086 and 0.0171 d-1, respectively, to yield the measurements of thyroidal iodine and physiological status of Korean adults. The determinedλ1andλ5values differed noticeably from the ICRP values, whereas theλ4value was comparable to that of the ICRP. Compared with the ICRP reference model, the Korean model, in which the Korean-specific transfer coefficients were adopted, predicted noticeably lower thyroidal uptake and faster decrease of thyroidal iodine. In addition, the predicted cumulative activities of radioiodine in the thyroid were substantially lower (40-80%) than those predicted by the ICRP model. The Korean model developed in this study demonstrates that the iodine biokinetics for Koreans (i.e. a population with a high iodine consumption) obviously differ from the prediction of the ICRP model. Hence, the Korean model may serve to improve the accuracy of thyroid dose estimation for Koreans and will lead to practical changes in matters concerned with radiological protection.

Risk perception of radiation emergency medical staff on low-dose radiation exposure: Knowledge is a critical factor.

Radiation emergency medical (REM) staff respond to many types of disasters such as radiological and nuclear accidents as well as environmental radioactivity exposure. The objective of this study was to evaluate the risk perception of REM staff on radiation exposure in various situations and to analyze the factors that affect their risk perception. A questionnaire was given to 284 REM staff affiliated with various organizations, including nuclear power generation, nuclear fuel manufacturing, large-scale irradiation, and radiation-waste disposal facilities, as well as research and development institutions. To determine the substantially influential factors for risk perception, we analyzed the questionnaire responses using ordinal logistic regression, Kruskal-Wallis, and Spearman correlation analyses. It was generally perceived by REM staff that low-dose radiation exposure in daily life and work environments does not pose any health risks. A higher level of radiation knowledge was tightly associated with a lower risk perception of REM staff on extremely low-dose (several mSv) radiation exposure, thus exhibiting an inverse correlation. In contrast to radiation researchers, the work experience of REM staff was not a contributing factor to their risk perception. In our study, REM staff with a high level of radiation knowledge did not have any health concerns in their work environments. Efforts to enhance the radiation knowledge of REM staff through proper education and training would result in analytical risk evaluation, which may also improve their willingness to help meet surge capacity needs in large-scale radiological events.

Role of Commensal Microbes in the γ-Ray Irradiation-Induced Physiological Changes in Drosophila melanogaster.

Ionizing radiation induces biological/physiological changes and affects commensal microbes, but few studies have examined the relationship between the physiological changes induced by irradiation and commensal microbes. This study investigated the role of commensal microbes in the γ-ray irradiation-induced physiological changes in Drosophila melanogaster. The bacterial load was increased in 5 Gy irradiated flies, but irradiation decreased the number of operational taxonomic units. The mean lifespan of conventional flies showed no significant change by irradiation, whereas that of axenic flies was negatively correlated with the radiation dose. γ-Ray irradiation did not change the average number of eggs in both conventional and axenic flies. Locomotion of conventional flies was decreased after 5 Gy radiation exposure, whereas no significant change in locomotion activity was detected in axenic flies after irradiation. γ-Ray irradiation increased the generation of reactive oxygen species in both conventional and axenic flies, but the increase was higher in axenic flies. Similarly, the amounts of mitochondria were increased in irradiated axenic flies but not in conventional flies. These results suggest that axenic flies are more sensitive in their mitochondrial responses to radiation than conventional flies, and increased sensitivity leads to a reduced lifespan and other physiological changes in axenic flies.

Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review.

Ionizing radiation (IR) is a high-energy radiation whose biological effects depend on the irradiation doses. Low-dose radiation (LDR) is delivered during medical diagnoses or by an exposure to radioactive elements and has been linked to the occurrence of chronic diseases, such as leukemia and cardiovascular diseases. Though epidemiological research is indispensable for predicting and dealing with LDR-induced abnormalities in individuals exposed to LDR, little is known about epidemiological markers of LDR exposure. Moreover, difference in the LDR-induced molecular events in each organ has been an obstacle to a thorough investigation of the LDR effects and a validation of the experimental results in in vivo models. In this review, we summarized the recent reports on LDR-induced risk of organ-specifically arranged the alterations for a comprehensive understanding of the biological effects of LDR. We suggested that LDR basically caused the accumulation of DNA damages, controlled systemic immune systems, induced oxidative damages on peripheral organs, and even benefited the viability in some organs. Furthermore, we concluded that understanding of organ-specific responses and the biological markers involved in the responses is needed to investigate the precise biological effects of LDR.

Rogue cell-like chromosomal aberrations in peripheral blood lymphocytes of interventional radiologists: A case study.

We report two cases of interventional radiologists who had been exposed to radiation while performing fluoroscopically-guided interventional procedures (FGIPs), mainly transcatheter arterial chemoembolization, percutaneous catheter drainage, and percutaneous transhepatic biliary drainage procedures, for over 10 years. They had a unique multi-aberrant cell type with not only high numbers of dicentrics and/or centric rings but also excess acentric double minutes, similar to a rogue cell. As revealed in a self-administered questionnaire, they wore personal dosimeters and protective equipment at all times and used shielding devices during interventional fluoroscopy procedures. However, the exposed dose levels derived from cytogenetic dosimetry were much higher than the doses recorded on their personal dosimeters. A large number of unstable and stable chromosomal aberrations that were found in the peripheral blood lymphocytes of these interventional radiologists might be due to repeated and long-term exposure to ionizing radiation while performing FGIPs. Further investigations of chromosomal aberrations in interventional radiologists may improve the understanding of the long-term effects of radiation exposure on medical personnel.

The Emerging Roles of Exosomes as EMT Regulators in Cancer.

Epithelial-mesenchymal transition (EMT) causes epithelial cells to lose their polarity and adhesion property, and endows them with migratory and invasive properties to enable them to become mesenchymal stem cells. EMT occurs throughout embryonic development, during wound healing, and in various pathological processes, including tumor progression. Considerable research in the last few decades has revealed that EMT is invariably related to tumor aggressiveness and metastasis. Apart from the interactions between numerous intracellular signaling pathways known to regulate EMT, extracellular modulators in the tumor microenvironment also influence tumor cells to undergo EMT, with extracellular vesicles (EVs) receiving increasing attention as EMT inducers. EVs comprise exosomes and microvesicles that carry proteins, nucleic acids, lipids, and other small molecules to stimulate EMT in cells. Among EVs, exosomes have been investigated in many studies, and their role has been found to be significant with respect to regulating intercellular communications. In this review, we summarize recent studies on exosomes and their cargoes that induce cancer-associated EMT. Furthermore, we describe the possible applications of exosomes as promising therapeutic strategies.

A Cohort Study of Korean Radiation Workers: Baseline Characteristics of Participants.

The Korean Radiation Worker Study investigated the health effects of protracted low-dose radiation among nuclear-related occupations in the Nuclear Safety and Security Commission in Korea. From 2016-2017, 20,608 workers were enrolled (86.5% men and 30.7% nuclear power plant workers). The mean cumulative dose ± standard deviation between 1984 and 2017 (1st quarter) was 11.8 ± 28.8 (range 0-417) mSv. Doses below recording level (≤0.1 mSv) were reported in 7901 (38.3%) cases; 431 (2%) had cumulative doses ≥100 mSv. From 1999-2016, 212 cancers (189 men, 23 women) occurred; thyroid cancer predominated (39.2%, 72 men, 11 women). In men, the standardized incidence ratio (SIR) for all cancers was significantly decreased (SIR = 0.76, 95% CI 0.66-0.88); however, that for thyroid cancer was significantly increased (SIR = 1.94, 95% CI 1.54-2.44). Compared to the non-exposed group (≤0.1 mSv), the relative risk (RR) in the exposed group (>0.1 mSv) after adjusting for sex, attained age, smoking status, and duration of employment was 0.82 (95% CI 0.60-1.12) for all cancers and 0.83 (95% CI 0.49-1.83) for thyroid cancer. The preliminary findings from this baseline study with a shorter follow-up than the latency period for solid cancer cannot exclude possible associations between radiation doses and cancer risk.

OCCUPATIONAL EXPOSURE CHARACTERISTICS AND FACTORS ASSOCIATED WITH RADIATION DOSES AMONG KOREAN RADIATION WORKERS.

This study identified occupational factors associated with radiation exposure in Korea. Survey data of 16 037 workers from 2016 to 2017, including lifestyle factors and occupational characteristics, were combined with the National Dose Registry. Higher average annual doses were observed in groups exhibiting health risk factors such as body mass index (BMI) and smoking. Average annual doses also differed according to occupational characteristics, including average daily working hours, use of radiation protection gear, calendar year of hiring and employment status. Moreover, the influence of different factors on radiation dose differed with occupations. In industrial radiography and nuclear power plants, average daily working hours were the most important factor determining worker radiation doses. In other occupations, such as education, industry and research, calendar year of hiring and duration of employment were the most important factors. This research indicates the need to consider the specific work procedures of occupations to determine exposure variations between or within facilities.

Evaluation of performance characteristics of portal monitor for radiation emergency.

For evaluating the counting efficiency of a portal monitor, we use a137Cs radiation point source (1 µCi) to subsequently establish it effective measurable area. Through simulation, we estimate the appropriate distance from potentially contaminated individuals in the scanning queue to the monitoring individual. When this distance is over 10 m, the counting efficiency was below 0.01%. We find that the triage can be applied to roughly 180 individuals per hour during mass casualties.

Assessment of working environment and personal dosimeter-wearing compliance of industrial radiographers based on chromosome aberration frequencies.

Industrial radiographers are exposed to relatively higher doses of radiation than other radiation-exposed workers in South Korea. The objective of our study was to investigate the impact of specific occupational conditions on chromosome aberration frequency and evaluate dosimeter-wearing compliance of industrial radiographers in Korea. We studied individual and occupational characteristics of 120 industrial radiographers working in South Korea and evaluated the frequency of dicentrics and translocations in chromosomes to estimate radiation exposure. The association between working conditions and chromosome aberration frequencies was assessed by Poisson regression analysis after adjusting for confounding factors. Legal personal dosimeter-wearing compliance among workers was investigated by correlation analysis between recorded dose and chromosome aberration frequency. Daily average number of radiographic films used in the last six months was associated with dicentrics frequency. Workers performing site radiography showed significantly higher translocation frequency than those working predominantly in shielded enclosures. The correlation between chromosome aberration frequency and recorded dose was higher in workers in the radiography occupation since 2012 (new workers) than other veteran workers. Our study found that site radiography could affect actual radiation exposure to workers. Controlling these working conditions and making an effort to improve personal dosimeter-wearing compliance among veteran workers as well as new workers may be necessary to reduce radiation exposure as much as possible in their workplace.

Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial.

PURPOSE: The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor-positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. PATIENTS AND METHODS: We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor-positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event. RESULTS: A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97; P = .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94; P = .029). CONCLUSION: The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.