Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Strengths and weaknesses of dosimetry used in studies of low-dose radiation exposure and cancer

Background A monograph systematically evaluating recent evidence on the dose-response relationship between low-dose ionizing radiation exposure and cancer risk required a critical appraisal of dosimetry methods in 26 potentially informative studies. Methods The relevant literature included studies published in 2006–2017. Studies comprised case-control and cohort designs examining populations predominantly exposed to sparsely ionizing radiation, mostly from external sources, resulting in average doses of no more than 100 mGy. At least two dosimetrists reviewed each study and appraised the strengths and weaknesses of the dosimetry systems used, including assessment of sources and effects of dose estimation error. An overarching concern was whether dose error might cause the spurious appearance of a dose-response where none was present. Results The review included 8 environmental, 4 medical, and 14 occupational studies that varied in properties relative to evaluation criteria. Treatment of dose estimation error also varied among studies, although few conducted a comprehensive evaluation. Six studies appeared to have known or suspected biases in dose estimates. The potential for these biases to cause a spurious dose-response association was constrained to three case-control studies that relied extensively on information gathered in interviews conducted after case ascertainment. Conclusions The potential for spurious dose-response associations from dose information appeared limited to case-control studies vulnerable to recall errors that may be differential by case status. Otherwise, risk estimates appeared reasonably free of a substantial bias from dose estimation error. Future studies would benefit from a comprehensive evaluation of dose estimation errors, including methods accounting for their potential effects on dose-response associations.</p

Doses d'irradiation reçues par les prématurés en service de réanimation

Purpose. Because of frequent radiological investigations performed in neonatal intensive care unit, a dosimetry study was carried out to assess the level of doses received by premature babies. Materials and methods. In vivo measurements were performed and effective doses were evaluated for single radiographs. Individual cumulative doses received over the period of stay were then estimated, for each premature baby entering the intensive care unit in 2002, taking into account the number of radiographs they underwent. Results. On average, babies stayed for a week and more than one radiograph was taken per day. Results showed that, even if average doses per radiograph were relatively low (25μSv), cumulative doses strongly depended on the length of stay, and can reach a few mSv. Conclusion. Even if doses per radiograph are in agreement with European recommendations, optimisation of doses is particularly important because premature babies are more sensitive to radiation than adults and because they usually undergo further radiological examinations in other services. On the basis of the results of this dosimetry study, the implementation of a larger study is being discussed. © Éditions Françaises de Radiologie, Paris, 2005

Patient radiation doses in paediatric interventional cardiology procedures A review

International audienceA large number of investigations into the radiation doses from x-ray guided interventional cardiology procedures in children have been carried out in recent years. A review was conducted of these studies, gathering data on kerma area product (P KA), fluoroscopic screening time (FT), air kerma, and estimates of effective dose and organ doses. The majority of studies focus on P KA and FT with no estimation of dose to the patient. A greater than ten-fold variation in average P KA was found between different studies, even where data were stratified by patient age or weight. Typical values of P KA were 0.6-10 Gy • cm2 (andlt;1 year/10 kg), 1.5-30 Gy • cm2 (1-5 years), 2-40 Gy • cm2 (5-10 years), 5-100 Gy • cm2 (10-16 years) and 10-200 Gy • cm2 (andgt;16 years). P KA was lowest for heart biopsy (0.3-10 Gy • cm2 for all ages combined) and atrial septostomy (0.4-4.0 Gy • cm2), and highest for pulmonary artery angioplasty (1.5-35 Gy • cm2) and right ventricular outflow tract dilatation (139 Gy • cm2). Most estimates of patient dose were in the form of effective dose (typically 3-15 mSv) which is of limited usefulness in individualised risk assessment. Few studies estimated organ doses. Despite advances in radiation protection, recent publications have reported surprisingly large doses, as represented by P KA and air kerma. There is little indication of a fall in these dose indicators over the last 15 years. Nor is there much suggestion of a fall in doses associated with the use of flat panel detectors, as opposed to image intensifiers. An assessment of the impact of radiation dose in the context of overall patient outcome is required. © 2016 IOP Publishing Ltd

Neurodevelopmental effects of low dose ionizing radiation exposure: A systematic review of the epidemiological evidence

Background: The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection. Objectives: We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment. Data sources: Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018. Study eligibility criteria: We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions. Study appraisal and synthesis methods: Studies were evaluated using the Cochrane Collaboration's risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed. Results: A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout. There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found. Limitations, conclusions, and implications of key findings: Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence. Systematic review registration number: The systematic review protocol was registered in PROSPERO (registration number CRD42018091902)