Epidemiological and experimental evidence for radiation-induced health effects in the progeny after exposure in utero.

Purpose: It has been known for many decades that radiation exposure of the developing embryo or fetus may cause two fundamentally different types of severe health effects: on the one hand, radiation may interfere with the normal intrauterine development, on the other hand, radiation may induce leukemia and cancer which become manifest in childhood. A large amount of epidemiological and experimental data has recently been presented which might be used to improve our understanding of underlying mechanisms and setting radiation protection standards. Yet, ecological studies in the populations exposed to increased levels of radiation in regions contaminated by radioactivity released from reactor accidents (Chernobyl, Fukushima) do not provide solid evidence which would contribute to this aim.

In vitro cellular and proteome assays identify Wnt pathway and CDKN2A-regulated senescence affected in mesenchymal stem cells from mice after a chronic LD gamma irradiation in utero.

Reliable data on the effects of chronic prenatal exposure to low dose (LD) of ionizing radiation in humans are missing. There are concerns about adverse long-term effects that may persist throughout postnatal life of the offspring. Due to their slow cell cycle kinetics and life-long residence time in the organism, mesenchymal stem cells (MSCs) are more susceptible to low level genotoxic stress caused by extrinsic multiple LD events.

Identifying a Diagnostic Window for the Use of Gene Expression Profiling to Predict Acute Radiation Syndrome.

In the event of a mass casualty radiological or nuclear scenario, it is important to distinguish between the unexposed (worried well), low-dose exposed individuals and those developing the hematological acute radiation syndrome (HARS) within the first three days postirradiation. In previous baboon studies, we identified altered gene expression changes after irradiation, which were predictive for the later developing HARS severity. Similar changes in the expression of four of these genes were observed using an in vitro human whole blood model.

Low-dose radiation therapy for COVID-19 pneumopathy: what is the evidence?

In the current dismal situation of the COVID-19 pandemic, effective management of patients with pneumonia and acute respiratory distress syndrome is of vital importance. Due to the current lack of effective pharmacological concepts, this situation has caused interest in (re)considering historical reports on the treatment of patients with low-dose radiation therapy for pneumonia. Although these historical reports are of low-level evidence per se, hampering recommendations for decision-making in the clinical setting, they indicate effectiveness in the dose range between 0.

Cancer immunology and radiobiology: Oliver Scott's struggle for the perfect tumour model in translational research.

Oliver Scott is best known for his research into the role of tumour hypoxia in radiation oncology. Yet no less important were Oliver's activities in the development of concepts and methods for performing translational research on the effect of ionising radiation on tumour in experimental animals, stressing the importance of using strictly inbred animals for transplantation of tumours which had arisen in exactly the identical mouse strain. Otherwise residual immunity would lead to uncontrollable bias in the results of cure experiments, invalidating conclusions.

Impact of Inter-Individual Variance in the Expression of a Radiation-Responsive Gene Panel Used for Triage.

In previous studies we determined a gene expression signature in baboons for predicting the severity of hematological acute radiation syndrome. We subsequently validated a set of eight of these genes in leukemia patients undergoing total-body irradiation. In the current study, we addressed the effect of intra-individual variability on the basal level of expression of those eight radiation-responsive genes identified previously, by examining baseline levels in 200 unexposed healthy human donors (122 males and 88 females with an average age of 46 years) using real-time PCR.

Successful Teaching of Radiobiology Students in the Medical Management of Acute Radiation Effects From Real Case Histories Using Clinical Signs and Symptoms and Taking Advantage of Recently Developed Software Tools.

In 2015, the Bundeswehr Institute of Radiobiology organized a North Atlantic Treaty Organization exercise to examine the significance of clinical signs and symptoms for the prediction of late-occurring acute radiation syndrome. Cases were generated using either the Medical Treatment Protocols for Radiation Accident Victims (METREPOL, n = 167) system or using real-case descriptions extracted from a database system for evaluation and archiving of radiation accidents based on case histories (SEARCH, n = 24). The cases ranged from unexposed [response category 0 (RC 0, n = 89)] to mild (RC 1, n = 45), moderate (RC 2, n = 19), severe (RC 3, n = 20), and lethal (RC 4, n = 18) acute radiation syndrome.

Education and training to support radiation protection research in Europe: the DoReMi experience.

A review is presented to the program of education and training setup within the DoReMi Network of Excellence. DoReMi was funded by Euratom under the EU 7th Framework Programme to coordinate the EU research into risks from low-dose ionizing radiation. It was seen to be necessary to form a network of expert institutions in order to tackle the scientific questions with the resources available.

Special radiobiological features of second cancer risk after particle radiotherapy.

In absolute terms: second cancer risks from radiotherapy of first cancers in adults are small compared to the benefits from radiotherapy but this is not so for radiotherapy of childhood cancers. Moreover, the radiation dose dependence of cancer induction differs between organs and tissues. The organ-specific dose dependence of second cancer risks may indicate the existence of different radiobiological mechanisms.

Master of Science (MSc) Program in Radiation Biology: An Interdepartmental Course Bridging the Gap between Radiation-Related Preclinical and Clinical Disciplines to Prepare Next-Generation Medical Scientists.

Radiation biology is a highly interdisciplinary field at the interface of biology, physics, and medicine. It is characterized by rapid advances in biological and technical knowledge. The potential for using these advances to optimize medical care, radiation protection, and related fields can be exploited only with complementary activities to support the education of young academics.

Tangential Field Radiotherapy for Breast Cancer-The Dose to the Heart and Heart Subvolumes: What Structures Must Be Contoured in Future Clinical Trials?

Background And Purpose: The aim of the present study was to evaluate if it is feasible for experienced radiation oncologists to visually sort out patients with a large dose to the heart. This would facilitate large retrospective data evaluations. And in case of an insufficient visual assessment, to define which structures should be contoured and which structures can be skipped as their dose can be derived from other easily contoured structures for future clinical trials.

Late proliferating and inflammatory effects on murine microvascular heart and lung endothelial cells after irradiation.

Background And Purpose: Radiotherapy of thoracic tumors increases the risk to develop cardiac diseases at later time-points. We compared time kinetics of radiation-induced changes of surface markers related to proliferation, progenitor cell development and inflammation in lung and heart microvascular endothelial cells (ECs).

Material And Methods: Mice received local thorax irradiation with a single dose of 0, 2 or 8 Gy.

Adhesion molecule expression and function of primary endothelial cells in benign and malignant tissues correlates with proliferation.

Background: Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs). This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization.

Methodology/principal Findings: Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively.

Cardiovascular effects after low-dose exposure and radiotherapy: what research is needed?

The authors of this report met at the Head Quarter of the International Atomic Energy Agency (IAEA) in Vienna, Austria, on 2-4 July 2012, for intensive discussions of an abundance of original publications on new epidemiological studies on cardiovascular effects after low-dose exposure and radiotherapy and radiobiological experiments as well as several comprehensive reviews that were published since the previous meeting by experts sponsored by the IAEA in June 2006. The data necessitated a re-evaluation of the situation with special emphasis on the consequences current experimental and clinical data may have for clinical oncology/radiotherapy and radiobiological research. The authors jointly arrived at the conclusions and recommendations presented here.

Second malignancies following breast cancer treatment: a case-control study based on the Peridose methodology. Allegro project (task 5.4).

Aims And Background: To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. MATERIAL AND STUDY DESIGN: A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed.

Are mouse lens epithelial cells more sensitive to γ-irradiation than lymphocytes?

In this pilot study we compared for the first time the radiation sensitivity of mouse lens epithelial cells (LECs) and mouse lymphocytes. We freshly prepared LECs and lymphocytes and irradiated them with γ-rays ((137)Cs; doses ranging from 0.25 to 2 Gy).

Biological mechanisms of normal tissue damage: importance for the design of NTCP models.

The normal tissue complication probability (NTCP) models that are currently being proposed for estimation of risk of harm following radiotherapy are mainly based on simplified empirical models, consisting of dose distribution parameters, possibly combined with clinical or other treatment-related factors. These are fitted to data from retrospective or prospective clinical studies. Although these models sometimes provide useful guidance for clinical practice, their predictive power on individuals seems to be limited.

The risks to healthy tissues from the use of existing and emerging techniques for radiation therapy.

As radical radiotherapy treatments become more effective, more and more cancer patients are becoming cured of their disease and surviving for decades. Damage to exposed healthy tissues that becomes manifest in the medium-to-long-term is becoming a more significant factor in the choice of individual treatment plans and treatment modality. However, currently there are no reliable objective methods for predicting in an individual patient the occurrence of normal tissue complications, or second cancers caused by radiation.