High-LET charged particles: radiobiology and application for new approaches in radiotherapy.

The number of patients treated with charged-particle radiotherapy as well as the number of treatment centers is increasing worldwide, particularly regarding protons. However, high-linear energy transfer (LET) particles, mainly carbon ions, are of special interest for application in radiotherapy, as their special physical features result in high precision and hence lower toxicity, and at the same time in increased efficiency in cell inactivation in the target region, i.e., the tumor. The radiobiology of high-LET particles differs with respect to DNA damage repair, cytogenetic damage, and cell death type, and their increased LET can tackle cells' resistance to hypoxia. Recent developments and perspectives, e.g., the return of high-LET particle therapy to the US with a center planned at Mayo clinics, the application of carbon ion radiotherapy using cost-reducing cyclotrons and the application of helium is foreseen to increase the interest in this type of radiotherapy. However, further preclinical research is needed to better understand the differential radiobiological mechanisms as opposed to photon radiotherapy, which will help to guide future clinical studies for optimal exploitation of high-LET particle therapy, in particular related to new concepts and innovative approaches. Herein, we summarize the basics and recent progress in high-LET particle radiobiology with a focus on carbon ions and discuss the implications of current knowledge for charged-particle radiotherapy. We emphasize the potential of high-LET particles with respect to immunogenicity and especially their combination with immunotherapy.

Immune checkpoint inhibitors and Carbon iON radiotherapy In solid Cancers with stable disease (ICONIC).

ICONIC is a multicenter, open-label, nonrandomized phase II clinical trial aiming to assess the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. The primary end point is objective response rate, and the secondary end points are safety, survival and disease control rate. Translational research is an exploratory aim. The planned sample size is 27 patients. The study combination will be considered worth investigating if at least four objective responses are observed. If the null hypothesis is rejected, ICONIC will be the first proof of concept of the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in oncology.

ICONIC is a multicenter, open-label, nonrandomized, phase II clinical trial aiming to evaluate the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. Considering that no clinical trials have been conducted thus far to assess the safety of the association between immune checkpoint inhibitors and carbon ion radiotherapy, the current clinical study will provide controlled data about the safety of this unprecedented therapeutic combination. Clinical Trial Registration: NCT05229614 (ClinicalTrials.gov).

Simulating Space Conditions Evokes Different DNA Damage Responses in Immature and Mature Cells of the Human Hematopoietic System.

The impact of space radiation and microgravity on DNA damage responses has been discussed controversially, largely due to the variety of model systems engaged. Here, we performed side-by-side analyses of human hematopoietic stem/progenitor cells (HSPC) and peripheral blood lymphocytes (PBL) cultivated in a 2D clinostat to simulate microgravity before, during and after photon and particle irradiation. We demonstrate that simulated microgravity (SMG) accelerates the early phase of non-homologous end joining (NHEJ)-mediated repair of simple, X-ray-induced DNA double-strand breaks (DSBs) in PBL, while repair kinetics in HSPC remained unaltered. Repair acceleration was lost with increasing LET of ion exposures, which increases the complexity of DSBs, precluding NHEJ and requiring end resection for successful repair. Such cell-type specific effect of SMG on DSB repair was dependent on the NF-кB pathway pre-activated in PBL but not HSPC. Already under unperturbed growth conditions HSPC and PBL suffered from SMG-induced replication stress associated with accumulation of single-stranded DNA and DSBs, respectively. We conclude that in PBL, SMG-induced DSBs promote repair of radiation-induced damage in an adaptive-like response. HSPC feature SMG-induced single-stranded DNA and FANCD2 foci, i.e., markers of persistent replication stress and senescence that may contribute to a premature decline of the immune system in space.

Particle radiotherapy and molecular therapies: mechanisms and strategies towards clinical applications.

Immunotherapy and targeted therapy are now commonly used in clinical trials in combination with radiotherapy for several cancers. While results are promising and encouraging, the molecular mechanisms of the interaction between the drugs and radiation remain largely unknown. This is especially important when switching from conventional photon therapy to particle therapy using protons or heavier ions. Different dose deposition patterns and molecular radiobiology can in fact modify the interaction with drugs and their effectiveness. We will show here that whilst the main molecular players are the same after low and high linear energy transfer radiation exposure, significant differences are observed in post-exposure signalling pathways that may lead to different effects of the drugs. We will also emphasise that the problem of the timing between drug administration and radiation and the fractionation regime are critical issues that need to be addressed urgently to achieve optimal results in combined treatments with particle therapy.

In-vivo dose determination in a human after radon exposure: proof of principle.

Radon-222 is pervasive in our environment and the second leading cause of lung cancer induction after smoking while it is simultaneously used to mediate anti-inflammatory effects. During exposure, radon gas distributes inhomogeneously in the body, making a spatially resolved dose quantification necessary to link physical exposure conditions with accompanying risks and beneficial effects. Current dose predictions rely on biokinetic models based on scarce input data from animal experiments and indirect exhalation measurements of a limited number of humans, which shows the need for further experimental verification. We present direct measurements of radon decay in the abdomen and thorax after inhalation as proof of principle in one patient. At both sites, most of the incorporated radon is removed within ~ 3 h, whereas a smaller fraction is retained longer and accounts for most of the deposited energy. The obtained absorbed dose values were [Formula: see text] µGy (abdomen, radon gas) and [Formula: see text] µGy (thorax, radon and progeny) for a one-hour reference exposure at a radon activity concentration of 55 kBq m-3. The accumulation of long-retained radon in the abdomen leads to higher dose values at that site than in the thorax. Contrasting prior work, our measurements are performed directly at specific body sites, i.e. thorax and abdomen, which allows for direct spatial distinction of radon kinetics in the body. They show more incorporated and retained radon than current approaches predict, suggesting higher doses. Although obtained only from one person, our data may thus represent a challenge for the barely experimentally benchmarked biokinetic dose assessment 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 0.3 and 1 Gy, similar to more recent dose concepts in the treatment of acute and chronic inflammatory/degenerative benign diseases with, e.g., a single dose per fraction of 0.5 Gy. This concise review aims to critically review the evidence for low-dose radiation treatment of COVID-19 pneumopathy and discuss whether it is worth investigating in the present clinical situation.

Radon Exposure-Therapeutic Effect and Cancer Risk.

Largely unnoticed, all life on earth is constantly exposed to low levels of ionizing radiation. Radon, an imperceptible natural occurring radioactive noble gas, contributes as the largest single fraction to radiation exposure from natural sources. For that reason, radon represents a major issue for radiation protection. Nevertheless, radon is also applied for the therapy of inflammatory and degenerative diseases in galleries and spas to many thousand patients a year. In either case, chronic environmental exposure or therapy, the effect of radon on the organism exposed is still under investigation at all levels of interaction. This includes the physical stage of diffusion and energy deposition by radioactive decay of radon and its progeny and the biological stage of initiating and propagating a physiologic response or inducing cancer after chronic exposure. The purpose of this manuscript is to comprehensively review the current knowledge of radon and its progeny on physical background, associated cancer risk and potential therapeutic effects.

Temporarily increased TGFß following radon spa correlates with reduced pain while serum IL-18 is a general predictive marker for pain sensitivity.

Sustained pain relief following radon spa therapy in patients suffering from chronic painful diseases has been well described. But still, the underlying mechanisms are not fully understood. We conducted the prospective and explorative RAD-ON01 study which included 103 patients who suffered from chronic painful musculoskeletal disorders of the spine and/or joints and present here the data of the examination of pro- and anti-inflammatory cytokines in the serum of the patients before and at weeks 6, 12 and 30 after therapy. While TNFα, IL-1ß, IFNγ, IL-1Ra and IL-10 were not altered, TGFß was temporarily significantly (p = 0.013) elevated 6 weeks after therapy. Importantly, this elevation positively correlated with lowered pain sensitivity (r = 0.41). Further, the amount of IL-18 in the serum positively correlated with lowered pain sensitivity. Therefore, IL-18 can be considered as predictive marker for pain sensitivity of radon spa patients. We conclude that alterations in TGFß and general IL-18 levels in serum have prognostic and predictive value in situations of lowered pain by exposure of patients to very low-doses of radiation as it is the case in radon spa.

Impact of radon and combinatory radon/carbon dioxide spa on pain and hypertension: Results from the explorative RAD-ON01 study.

OBJECTIVES: Therapies with low doses of radon have beneficial effects on patients suffering from chronic painful degenerative and inflammatory diseases. We already showed that this is accompanied by systemic immune modulations. We here focus on pain-reducing effects of very low doses of radon by adding carbon dioxide water and its impact on heart rate variability (HRV), blood pressure and free radicals. METHODS: 97 of 103 patients receiving radon spa (1.200 Bq/l at 34 °C or 600 Bq/l, 1 g/l CO2 at 34 °C) were monitored before and at three different time points after therapy. Individual pain perception was analyzed and the capability to process radicals. At each time point, the hypertensive patients (n = 46) were examined over 24 h for blood pressure and HRV. RESULTS: Long-term pain reduction was observed in the majority of patients. A modulation of superoxide dismutase was identified, presumably representing a priming effect for lowering radiation stress. Further, lowering of blood pressure, especially in those patients who additionally received carbon dioxide, was seen. Radon did in particular impact on HRV implying lasting relaxation effects. CONCLUSION: Radon/carbon dioxide spa efficiently reduces pain. In particular, patients simultaneously suffering from painful and cardiovascular diseases should be treated by combination of radon and CO2.

Impact of X-ray Exposure on the Proliferation and Differentiation of Human Pre-Adipocytes.

Radiotherapy is a widely used treatment option for cancer patients as well as for patients with musculoskeletal disorders. Adipocytes, the dominant cell type of adipose tissue, are known to constitute an active part of the tumor microenvironment. Moreover, adipocytes support inflammatory processes and cartilage degradation in chronic inflammatory diseases, i.e., rheumatoid and osteoarthritis. Since the production of inflammatory factors is linked to their differentiation stages, we set out to explore the radiation response of pre-adipocytes that may influence their inflammatory potential and differentiation capacity. This is the first study investigating the effects of X-ray irradiation on the proliferation and differentiation capacity of human primary pre-adipocytes, in comparison to Simpson⁻Golabi⁻Behmel Syndrome (SGBS) pre-adipocytes, an often-used in vitro model of human primary pre-adipocytes. Our results demonstrate a dose-dependent reduction of the proliferation capacity for both cell strains, whereas the potential for differentiation was mostly unaffected by irradiation. The expression of markers of adipogenic development, such as transcription factors (PPARγ, C/EBPα and C/EBPß), as well as the release of adipokines (visfatin, adiponectin and leptin) were not significantly changed upon irradiation. However, after irradiation with high X-ray doses, an increased lipid accumulation was observed, which suggests a radiation-induced response of adipocytes related to inflammation. Our results indicate that pre-adipocytes are radio-resistant, and it remains to be elucidated whether this holds true for the overall inflammatory response of adipocytes upon irradiation.

Radiation-Induced Endothelial Inflammation Is Transferred via the Secretome to Recipient Cells in a STAT-Mediated Process.

Radiation is the most common treatment of cancer. Minimizing the normal tissue injury, especially the damage to vascular endothelium, remains a challenge. This study aimed to analyze direct and indirect radiation effects on the endothelium by investigating mechanisms of signal transfer from irradiated to nonirradiated endothelial cells by means of secreted proteins. Human coronary artery endothelial cells (HCECest2) undergo radiation-induced senescence in vitro 14 days after exposure to 10 Gy X-rays. Proteomics analysis was performed on HCECest2 14 days after irradiation with X-ray doses of 0 Gy (control) or 10 Gy using label-free technology. Additionally, the proteomes of control and radiation-induced secretomes, and those of nonirradiated HCECest2 exposed for 24 h to secreted proteins of either condition were measured. Key changes identified by proteomics and bioinformatics were validated by immunoblotting, ELISA, bead-based multiplex assays, and targeted transcriptomics. The irradiated cells, their secretome, and the nonirradiated recipient cells showed similar inflammatory response, characterized by induction of interferon type I-related proteins and activation of the STAT3 pathway. These data indicate that irradiated endothelial cells may adversely affect nonirradiated surrounding cells via senescence-associated secretory phenotype. This study adds to our knowledge of the pathological background of radiation-induced cardiovascular disease.

Low-dose photon irradiation alters cell differentiation via activation of hIK channels.

To understand the impact of ionizing irradiation from diagnostics and radiotherapy on cells, we examined K(+) channel activity before and immediately after exposing cells to X-rays. Already, low dose in the cGy range caused in adenocarcinoma A549 cells within minutes a hyperpolarization following activation of the human intermediate-conductance Ca(2+)-activated K(+) channel (hIK). The response was specific for cells, which functionally expressed hIK channels and in which hIK activity was low before irradiation. HEK293 cells, which do not respond to X-ray irradiation, accordingly develop a sensitivity to this stress after heterologous expression of hIK channels. The data suggest that hIK activation involves a Ca(2+)-mediated signaling cascade because channel activation is suppressed by a strong cytosolic Ca(2+) buffer. The finding that an elevation of H2O2 causes an increase in the concentration of cytosolic Ca(2+) suggests that radicals, which emerge early in response to irradiation, trigger this Ca(2+) signaling cascade. Inhibition of hIK channels by specific blockers clotrimazole and TRAM-34 slowed cell proliferation and migration in "wound" scratch assays; ionizing irradiation, in turn, stimulated the latter process presumably via its activation of the hIK channels. These data stress an indirect radiosensitivity of hIK channels with an impact on cell differentiation.

Study of the anti-inflammatory effects of low-dose radiation: The contribution of biphasic regulation of the antioxidative system in endothelial cells.

BACKGROUND: We examined (a) the expression of the antioxidative factor glutathione peroxidase (GPx) and the transcription factor nuclear factor E2-related factor 2 (Nrf2) following low-dose X-irradiation in endothelial cells (ECs) and (b) the impact of reactive oxygen species (ROS) and Nrf2 on functional properties of ECs to gain further knowledge about the anti-inflammatory mode of action of low doses of ionizing radiation. MATERIAL AND METHODS: EA.hy926 ECs and primary human dermal microvascular ECs (HMVEC) were stimulated by tumor necrosis factor-α (TNF-α, 20 ng/ml) 4 h before irradiation with single doses ranging from 0.3 to 3 Gy. The expression and activity of GPx and Nrf2 were analyzed by flow cytometry, colorimetric assays, and real-time PCR. The impact of ROS and Nrf2 on peripheral blood mononuclear cell (PBMC) adhesion was assayed in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and Nrf2 activator AI-1. RESULTS: Following a low-dose exposure, we observed in EA.hy926 EC and HMVECs a discontinuous expression and enzymatic activity of GPx concomitant with a lowered expression and DNA binding activity of Nrf2 that was most pronounced at a dose of 0.5 Gy. Scavenging of ROS by NAC and activation of Nrf2 by AI-1 significantly diminished a lowered adhesion of PBMC to EC at a dose of 0.5 Gy. CONCLUSION: Low-dose irradiation resulted in a nonlinear expression and activity of major compounds of the antioxidative system that might contribute to anti-inflammatory effects in stimulated ECs.

Carbon ion radiotherapy of human lung cancer attenuates HIF-1 signaling and acts with considerably enhanced therapeutic efficiency.

Carbon ion irradiation is an emerging therapeutic option for various tumor entities. Radiation resistance of solid tumors toward photon irradiation is caused by attenuation of DNA damage in less oxygenated tumor areas and by increased hypoxia-inducible factor (HIF)-1 signaling. Carbon ion irradiation acts independently of oxygen; however, the role of HIF-1 is unclear. We analyzed the effect of HIF-1 signaling after carbon ions in comparison to photons by using biological equivalent radiation doses in a human non-small-cell cancer model. The studies were performed in cultured A549 and H1299 cell lines and in A549 xenografts. Knockdown of HIF-1α in vivo combined with photon irradiation delayed tumor growth (23 vs. 13 d; P<0.05). Photon irradiation induced HIF-1α and target genes, predominantly in oxygenated cells (1.6-fold; P<0.05), with subsequent enhanced tumor angiogenesis (1.7-fold; P<0.05). These effects were not observed after carbon ion irradiation. Micro-DNA array analysis indicated that photons, but not carbon ions, significantly induced components of the mTOR (mammalian target of rapamycin) pathway (gene set enrichment analysis; P<0.01) as relevant for HIF-1α induction. After carbon ion irradiation in vivo, we observed substantially decreased HIF-1α levels (8.9-fold; P<0.01) and drastically delayed tumor growth (P<0.01), an important finding that indicates a higher relative biological effectiveness (RBE) than anticipated from the cell survival data. Taken together, the evidence showed that carbon ions mediate an improved therapeutic effectiveness without tumor-promoting HIF-1 signaling.

[Perinatal vulnerability and social-support during the postnatal period: a review of the literature]. / Vulnérabilité périnatale et soutien social en période postnatale : une revue de la littérature.

OBJECTIVE: To present the results of an integrative review of the literature that summarized empirical knowledge on dimensions of vulnerability during the perinatal period leading to informal and semi-formal postnatal support needs. METHOD: The literature search was performed in ten databases, covering the period from 1990 to March 2013. Relevant information was extracted and analysed in an integrative mode according to four main vulnerability dimensions: biological, psychological, social, cognitive. RESULTS: Thirty studies were included. Biological vulnerabilities mainly concern tiredness and breastfeeding difficulties; psychological vulnerabilities consist of stress, feelings of parental incompetence and need for reassurance; social vulnerabilities comprise performance pressure concerning new responsibilities and entertainment needs, instrumental assistance and peer social support; and cognitive vulnerabilities correspond to a need for participatory information on the prenatal period from peers. CONCLUSION: The transition to parenthood is an important step during which individuals may experience a state of vulnerability with numerous and interconnected dimensions. The variousforms of postnatal support therefore need to be harmonised in order to support parents. Research is needed on the harmonisation of the various support networks, which raises significant challenges, especially in terms of resources, funding, and information exchange, that must be documented.

Discriminating bloom-forming cyanobacteria using lab-based hyperspectral imagery and machine learning: Validation with toxic species under environmental ranges.

Cyanobacteria are major contributors to algal blooms in inland waters, threatening ecosystem function and water uses, especially when toxin-producing strains dominate. Here, we examine 140 hyperspectral (HS) images of five representatives of the widespread, potentially toxin-producing and bloom-forming genera Microcystis, Planktothrix, Aphanizomenon, Chrysosporum and Dolichospermum, to determine the potential of utilizing visible and near-infrared (VIS/NIR) reflectance for their discrimination. Cultures were grown under various light and nutrient conditions to induce a wide range of pigment and spectral variability, mimicking variations potentially found in natural environments. Importantly, we assumed a simplified scenario where all spectral variability was derived from cyanobacteria. Throughout the cyanobacterial life cycle, multiple HS images were acquired along with extractions of chlorophyll a and phycocyanin. Images were calibrated and average spectra from the region of interest were extracted using k-means algorithm. The spectral data were pre-processed with seven methods for subsequent integration into Random Forest models, whose performances were evaluated with different metrics on the training, validation and testing sets. Successful classification rates close to 90 % were achieved using either the first or second derivative along with spectral smoothing, identifying important wavelengths in both the VIS and NIR. Microcystis and Chrysosporum were the genera achieving the highest accuracy (>95 %), followed by Planktothrix (79 %), and finally Dolichospermum and Aphanizomenon (>50 %). The potential of HS imagery to discriminate among toxic cyanobacteria is discussed in the context of advanced monitoring, aiming to enhance remote sensing capabilities and risk predictions for water bodies affected by cyanobacterial harmful algal blooms.

Carbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models.

PURPOSE: Personalized liposome-formulated mRNA vaccines (RNA-LPX) are a powerful new tool in cancer immunotherapy. In preclinical tumor models, RNA-LPX vaccines are known to achieve potent results when combined with conventional X-ray radiation therapy (XRT). Densely ionizing radiation used in carbon ion radiation therapy (CIRT) may induce distinct effects in combination with immunotherapy compared with sparsely ionizing X-rays. METHODS AND MATERIALS: Within this study, we investigate the potential of CIRT and isoeffective doses of XRT to mediate tumor growth inhibition and survival in murine colon adenocarcinoma models in conjunction with neoantigen (neoAg)-specific RNA-LPX vaccines encoding both major histocompatibility complex (MHC) class I- and class II-restricted tumor-specific neoantigens. We characterize tumor immune infiltrates and antigen-specific T cell responses by flow cytometry and interferon-γ enzyme-linked immunosorbent spot (ELISpot) analyses, respectively. RESULTS: NeoAg RNA-LPX vaccines significantly potentiate radiation therapy-mediated tumor growth inhibition. CIRT and XRT alone marginally prime neoAg-specific T cell responses detected in the tumors but not in the blood or spleens of mice. Infiltration and cytotoxicity of neoAg-specific T cells is strongly driven by RNA-LPX vaccines and is accompanied by reduced expression of the inhibitory markers PD-1 and Tim-3 on these cells. The neoAg RNA-LPX vaccine shows similar overall therapeutic efficacy in combination with both CIRT and XRT, even if the physical radiation dose is lower for carbon ions than for X-rays. CONCLUSIONS: We hence conclude that the combination of CIRT and neoAg RNA-LPX vaccines is a promising strategy for the treatment of radioresistant tumors.

Radiation-induced DNA double-strand breaks in cortisol exposed fibroblasts as quantified with the novel foci-integrated damage complexity score (FIDCS).

Without the protective shielding of Earth's atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities.

p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation.

BACKGROUND: To determine whether ceramide is responsible for the induction of p53-independent early or late apoptosis in response to high- and low-Linear-Energy-Transfer (LET) irradiation. METHODS: Four cell lines displaying different radiosensitivities and p53-protein status were irradiated with photons or 33.4 or 184 keV/µm carbon ions. The kinetics of ceramide production was quantified by fluorescent microscopy or High-Performance-Liquid-Chromatogaphy and the sequence of events leading to apoptosis by flow cytometry. RESULTS: Regardless of the p53-status, both low and high-LET irradiation induced an early ceramide production in radiosensitive cells and late in the radioresistant. This production strongly correlated with the level of early apoptosis in radiosensitive cells and delayed apoptosis in the radioresistant ones, regardless of radiation quality, tumor type, radiosensitivity, or p53-status. Inhibition of caspase activity or ceramide production showed that, for both types of radiation, ceramide is essential for the initiation of early apoptosis in radiosensitive cells and late apoptosis following mitotic catastrophe in radioresistant cells. CONCLUSIONS: Ceramide is a determining factor in the onset of early and late apoptosis after low and high-LET irradiation and is the mediator of the p53-independent-apoptotic pathway. We propose that ceramide is the molecular bridge between mitotic catastrophe and the commitment phase of delayed apoptosis in response to irradiation.

Radon progeny measurements in a ventilated filter system to study respiratory-supported exposure.

Radon (222Rn) and its progeny are responsible for half of the annual dose from natural radiation and the most frequent cause for lung cancer induction after smoking. During inhalation, progeny nuclides accumulate in the respiratory tract while most of the radon gas is exhaled. The decay of progeny nuclides in the lung together with the high radiosensitivity of this tissue lead to equivalent doses implying a significant cancer risk. Here, we use gamma spectroscopy to measure the attachment of radon progeny on an air-ventilated filter system within a radon enriched atmosphere, mimicking the respiratory tract. A mathematical model was developed to describe the measured time-dependent activities of radon progeny on the filter system. We verified a linear relation between the ambient radon activity concentration during exposure and the amount of decay products on the filter system. The measured activities on the filters and its mathematical description are in good agreement. The developed experimental set-up can thus serve to further investigate the deposition of radon progeny in the respiratory tract under varying conditions for determination of dose conversion factors in radiation protection, which we demonstrate by deriving dose estimations in mouse lung.