Objective: To investigate the potential impact of two different combinations of neutron and gamma radiation on gene expression and dicentric chromosomes in peripheral blood mononuclear cells (PBMC).

Methods: Whole blood from 3 human donors was exposed to neutrons with an energy spectrum similar to that of the Hiroshima uranium bomb, to gamma radiation from a ⁶⁰Co source and to a 50:50 combination of both radiations, given in two orders of sequence. In all cases the total doses were 0.5, 0.75 and 1.0 ​Gy. Dicentric chromosomes were analyzed by light microscopy and the expression of six known radiation-responsive genes BBC3, CDKN1A, FDXR, GADD45A, MDM2, and XPC were analyzed by RT-qPCR.

Results: Per unit dose, exposure to neutrons lead to a higher level of dicentrics and gene expression as compared to gamma radiation. Dose-response relationships for both endpoints were linear, allowing calculating the expected outcome of combined exposure by arithmetic. For dicentric chromosomes, the RBE values for ⁶⁰Co → neutrons, neutrons → ⁶⁰Co and neutrons were 4.05, 3.62 and 7.30, respectively. For gene expression the RBE values were gene-specific, but showed values in the range of 1.14–3.01 for ⁶⁰Co → neutrons, 1.33–2.68 for neutrons → ⁶⁰Co and 1.39–3.91 for neutrons.

Conclusions: The results demonstrate that combined exposure to neutrons and gamma radiation, regardless of the order of sequence, leads to an additive response at both endpoints. This indicates that calibration curves for mixed beams can be constructed from dose response relationships of the single beam components.

The role of genetics in susceptibility to radiotherapy-induced toxicities is unclear. A strong impact of genetics should cause correlated toxicities in patients with metachronous double radiotherapy. We ascertained information about demographics, lifestyle, radiotherapy and early toxicities in irradiated tissues for a retrospective cohort of 98 patients from 2 hospitals who underwent two metachronous radiotherapeutic treatments (2000-2022) of different anatomical regions. European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) toxicity scores per organ system were combined to a single mean score. We considered as genetic component the variation of toxicity not explained by radiation dose to the tumor, age at radiotherapy, sex, smoking status, and surgery. Variance components of toxicity were evaluated by ordinal logistic regression with random intercept. Common site combinations were breast/contralateral breast (N = 16), breast/ endometrium (N = 6), and cervix/breast (N = 5). Mean toxicity over exposed tissues was 0.70 (range, 0-3). Prescribed radiation dose was significantly associated with mean toxicity, with a 5% (95% CI 3-8) increase of the odds for a higher toxicity level per Gy. Sex, surgery, age and smoking were not. There was no genetic contribution to risk of toxicities after adjustment. Toxicity levels were not more similar within patients than between patients, suggesting a negligible impact of genotype on radiotherapy-related toxicities.

Background: Cancer bone metastasis (BM) from castration-resistant prostate cancer (CRPC) is the terminal stage of cancer, and it demonstrates a decreasing quality of life (QOL) due to skeletal-related events such as pain and bone fracture. Radium-223 dichloride administration is frequently selected as an internal radionuclide target therapy. This radioactive molecule has a potency of accumulation in bone minerals and emits alpha particles by decaying radium-223. These physical properties cause cellular damage to bone metastatic CRPC cells. However, some poor outcomes of patients are occasionally observed, such as bone marrow suppression. Therefore, in order to understand the status of deep BM, it is necessary to discover biomarkers that effectively reflect bone metabolism. In this study, we investigated whether urinal 8-hydroxy-2'-deoxyguanosine (8-OHdG), a one of oxidative stress marker, could be a predictive biomarker to identify whether radium-223 administration causes bone marrow suppression in patients.

Methods: The urine and blood serum from four cancer patients with BM were collected and stored at −80 ℃ deep freezer until analysis. Following radiotherapeutic guidelines, three to six radium-223 internal radiotherapy doses were prescribed based on the patient, and it was terminated due to decreased therapeutic reserve.

Results: The patients who were administered six radium-223 doses demonstrated upregulation of urinal 8-OHdG, serum C-terminal telopeptide of type I collagen (1CTP), and type I collagen cross-linked N-telopeptide (NTX) concentrations. Conversely, serum bone alkaline phosphatase (BAP) was downregulated. The patients who were administered less than five radium-223 doses exhibited urinal 8-OHdG downregulation and similar serum 1CTP, NTX, and BAP levels compared to before administration. In the patient who had bone marrow suppression, a negative correlation between time after first administration of radium-223 and urinal 8-OHdG was observed.

Conclusions: These results suggest that a urinal 8-OHdG concentration has a potency of biomarker for bone marrow suppression under the administration of radium-223 in the patient with BM from CRPC.

Radiation protection is a cornerstone of public health, occupational safety, patient welfare, and environmental stewardship. A strong emphasis on radiation protection is necessary to contribute to the well-being of citizens, to innovation and sustainable growth across Europe, and to meet the challenges by application of new technologies, and emerging threats. While the use of ionising radiation and radioactive substances underpins significant advancements in medicine, nuclear and non-nuclear industry, it also poses risks that must be carefully defined and managed in environmental and health policies. Effective radiation protection knowledge and know-how help balance the benefits and risks of ionising radiation use, empowering European society to harness its potential safely. Neglecting investment in radiation protection research could lead to increased risks, delayed innovation, and risk-disproportionate radiation protection policy and regulation frameworks, hindering Europe's progress and resilience. This white paper argues for sustained investment in radiation protection research, in the follow-up of the dedicated PIANOFORTE pan-European partnership (2022–2029). In the context of the 10th Framework Programme of Research and Innovation and its related EURATOM's part, this should be achieved with a funding envelop for radiation protection research of ca. 75 M€ through a PIANOFORTE-like partnership, including actions related to infrastructure and education and training. Such investment forms an essential component of Europe's strategy for competitiveness, security, and quality of life, including quality of environmental resources and natural capital, notably but not only in the context of the energy transition. Key challenges related to occupational exposure, medical diagnostics and treatments, emergency preparedness and response, exposure to natural sources of radiation and environmental protection underscore the need for comprehensive research to support evidence-based policy decisions, harmonised regulations and safe, sustainable and integrated practices that address protection of both human and environmental health.

Breast cancer is the most common cancer globally in terms of incidence. This cancer is classified into subtypes based on histological or immunological characteristics. HER2-positive cases account for 15-25% of breast cancer cases, and one of the first events in breast carcinogenesis is HER2 upregulation. Furthermore, HER2 expression increases the detection rate of metastatic or recurrent breast cancers by 50-80%. The epidermal growth factor receptor family includes HER2, which is a transmembrane receptor protein. In our previous case report, patients who were resistant to anti-HER2 monoclonal antibody therapy, chemotherapy and radiotherapy had higher concentrations of phospholipid metabolites such as phosphatidylcholine and sphingomyelin (SM), which was associated with cancer recurrence progression. To better understand the relationship between radiotherapy resistance and SM expression, breast cancer cell lines with and without HER2 expression (MCF7 and BT474) after exposure to ionizing radiation (IR) were examined. In the cell culture supernatant, similar levels of SM in MCF7 cells were identified after 1-4 Gy exposure. However, SM levels in BT474 cells were upregulated compared with those of in the control group. Intracellular SM levels were upregulated in BT474 cells exposed to 1 and 4 Gy compared with the non-irradiated control group. Furthermore, significantly increased mRNA expression levels of sphingomyelin synthase 2 (SGMS2) in BT474 cells exposed to IR were observed compared with those in nonirradiated cells; however, the SGMS2 levels in MCF7 cells did not differ significantly among the 0, 2 and 4 Gy groups. These findings suggested that a higher dose of IR induced the secretion of SM and its associated gene expression in HER2-positive breast cancer cells.

Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0–2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.

Reliable dosimetry systems are crucial for radiobiological experiments either to quantify the biological consequences of ionizing radiation or to reproduce results by other laboratories. Also, they are essential for didactic purposes in the field of radiation research. Professional dosemeters are expensive and difficult to use in exposure facilities with closed exposure chambers. Consequently, a simple, inexpensive, battery-driven dosemeter was developed that can be easily built using readily available components. Measurements were performed to validate its readout with photons of different energy and dose rate and to demonstrate the applicability of the dosemeter. It turned out that the accuracy of the dose measurements using the developed dosemeter was better than 10%, which is satisfactory for radiobiological experiments. It is concluded that this dosemeter can be used both for determining the dose rates of an exposure facility and for educational purposes. 

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0 Gy to 4 Gy at two different facilities in Germany (PTB) and USA (CINF). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semi-automatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semi-automatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed non-linear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts.

The necessity of precise dosimetry and its documentation in research is less obvious than in medicine and in radiological protection. However, in radiation research, results can only be validated if experiments were carried out with sufficient precision and described with sufficient details, especially information regarding dosimetry. In order to ensure this, an initiative was launched to establish reproducible dosimetry reporting parameters in published studies. Minimum standards for reporting radiation dosimetry information were developed and published in parallel in the International Journal of Radiation Biology and Radiation Research. As editors of Radiation and Environmental Biophysics, we support this initiative and reproduce the agreed minimum irradiation parameters that should be reported in publications on radiation biology submitted to our journal.