Comparison of biochemical changes induced in radioresistant prostate cancer cells by X-rays, radiosensitizing drugs, and a combined therapy using Raman microspectroscopy.

Cancer radioresistance is a major problem in radiotherapy. Many strategies have been proposed to overcome this process including the use of radiosensitizing drugs such as C75 or silibinin. The overall result of all treatments (radiotherapy, chemotherapy, and combined treatment) is cancer cell death. On the other hand, each treatment affects cancer cells differently at the molecular level. However, little is known about biochemical changes induced in cancer cells by these treatments (especially in combined therapy) at the submicroscale. In this study, Raman microspectroscopy was applied to follow such changes induced in radioresistant prostate cancer cells by X-rays, radiosensitizing drugs (C75, silibinin), and a combined treatment. The analysis was supported by the Partial Least Squares Regression method to reveal spectral changes induced by an increasing dose of X-rays and concentrations of the drugs. The obtained regression coefficient (ß) plots were compared to each other using a correlation coefficient (R). Our results show that PC-3 cells exhibit dose- and concentration-dependent responses to the treatment with different biochemical changes induced by X-rays in the presence of C75 and silibinin. Moreover, both drugs affect the cells differently at the submicroscale and independently from the X-ray's presence. Finally, C75 shows significant efficiency in the reduction of cell radioresistance.

Efficient enhancement of the antimicrobial activity of Chlamydomonas reinhardtii extract by transgene expression and molecular modification using ionizing radiation.

BACKGROUND: Ionizing radiation has been used for mutagenesis or material modification. The potential to use microalgae as a platform for antimicrobial production has been reported, but little work has been done to advance it beyond characterization to biotechnology. This study explored two different applications of ionizing radiation as a metabolic remodeler and a molecular modifier to enhance the antimicrobial activity of total protein and solvent extracts of Chlamydomonas reinhardtii cells. RESULTS: First, highly efficient transgenic C. reinhardtii strains expressing the plant-derived antimicrobial peptides, AtPR1 or AtTHI2.1, were developed using the radiation-inducible promoter, CrRPA70Ap. Low transgene expression was significantly improved through X-irradiation (12-50 Gy), with peak activity observed within 2 h. Protein extracts from these strains after X-irradiation showed enhanced antimicrobial activity against the prokaryotic bacterium, Pseudomonas syringae, and the eukaryotic fungus, Cryptococcus neoformans. In addition, X-irradiation (12 Gy) increased the growth and biomass of the transgenic strains. Second, C. reinhardtii cell extracts in ethanol were γ-irradiated (5-20 kGy), leading to molecular modifications and increased antimicrobial activity against the phytopathogenic bacteria, P. syringae and Burkholderia glumae, in a dose-dependent manner. These changes were associated with alterations in fatty acid composition. When both transgenic expression of antimicrobial peptides and molecular modification of bioactive substances were applied, the antimicrobial activity of C. reinhardtii cell extracts was further enhanced to some extent. CONCLUSION: Overall, these findings suggest that ionizing radiation can significantly enhance the antimicrobial potential of C. reinhardtii through efficient transgene expression and molecular modification of bioactive substances, making it a valuable source of natural antimicrobial agents. Ionizing radiation can act not only as a metabolic remodeler of transgene expression in microalgae but also as a molecular modifier of the bioactive substances.

Ionizing radiation effects on blood-derived extracellular vesicles: insights into miR-34a-5p-mediated cellular responses and biomarker potential.

Adverse effects of ionizing radiation on normal tissues limit the radiation dose in cancer treatment, thereby compromising treatment efficiency. Among the consistently affected non-cancer cells, peripheral blood mononuclear cells (PBMCs) exhibit high radiosensitivity and have the potential to induce systemic effects. PBMC-released extracellular vesicles (EVs), contribute to the communication of such systemic effects. This study aimed to investigate the effects of ionizing radiation on EVs as part of the systemic response of PBMCs in terms of microRNA cargo and biological functions.Therefore, whole blood samples from healthy donors were irradiated ex-vivo (0 Gy, 1 Gy, 2 Gy, 4 Gy) and EVs from PBMCs were isolated after 96 h by PEG precipitation or ultracentrifugation. Candidate microRNAs were examined in PBMC-derived EVs from individual donors. The uptake of membrane-stained fluorescent EVs by different recipient cells was quantified by fluorescence-activated cell sorting analysis. The biological effects of increased miR-34a-5p and of total EVs on recipient cells were assessed.Irradiation of PBMCs induced a dose-dependent upregulation of miR-34a-5p within EVs and PBMCs. However, interindividual differences between donors were noticed in the extent of upregulation, and small EVs displayed more pronounced changes in microRNA levels in comparison to large EVs. Irradiation in presence of the small molecule inhibitor KU-60019 demonstrated that this upregulation is dependent on ATM (Ataxia telangiectasia mutated) activation. Moreover, fibroblasts and keratinocytes were identified as preferred EV recipients. Increased miR-34a-5p levels led to a significant reduction in viability and induction of senescence in keratinocytes but not in fibroblasts, indicating a cell type-specific response.In conclusion, this study further elucidated the complex cellular response of normal tissue after radiation exposure. It confirmed radiation-induced modifications of microRNA expression levels in EVs from PBMCs and identified a robust upregulation of miR-34a-5p in the small EV subfraction, suggesting this microRNA as a potential novel candidate for the development of biomarkers for radiation exposure. Moreover, the different uptake efficiencies observed among specific cell types suggested that EVs induce cell type-specific responses in the intercellular communication of systemic radiation effects.

[Analysis of the results of personal monitoring to ionizing radiation at workplaces]. / Analiza wyników rutynowego monitoringu narazenia personelu na promieniowanie jonizujace w miejscach pracy.

BACKGROUND: The paper presents the results of dosimetric measurements routinely performed by the Radiation Protection Department of the Nofer Institute of Occupational Medicine (NIOM) in Lódz in 2022 for people occupationally exposed to X and γ radiation. MATERIAL AND METHODS: The evaluation of the effective dose as part of individual dosimetry was provided using the film or thermoluminescent dosimetry (TLD). Additionally, based exclusively on the TLD method, measurements of the ambient dose equivalent H*(10) and personal dose equivalents Hp(0.07) and Hp(3) were performed. In 2022, the dosimetric service of the Radiological Protection Department of the NIOM covered >30 000 workers employed in >4500 laboratories (mainly health care departments). All measurements were performed in accordance with accredited research procedures (number AB 327). RESULTS: In 2022, the average annual dose of Hp(10) was equal to 0.26 mSv, whereas Hp(0.07) measured using ring and wrist dosimetry was equal to 0.63 mSv and 0.78 mSv, respectively. In turn, the average Hp(3) value was 0.21 mSv. In 2022, there was not a single case of exceeding the annual dose limit among people measured by the NIOM. CONCLUSIONS: The data collected in the "Dosimetry" database of the NIOM and a detailed analysis of annual doses received by people occupationally exposed to ionizing radiation indicate a well-functioning radiological protection system in Poland. Med Pr Work Health Saf. 2024;75(5).

Immunological signatures from irradiated cancer-associated fibroblasts.

Introduction: Cancer-associated fibroblasts (CAFs) are abundant and influential elements of the tumor microenvironment (TME), giving support to tumor development in multiple ways. Among other mechanisms, CAFs are important regulators of immunological processes occurring in tumors. However, CAF-mediated tumor immunomodulation in the context of radiotherapy remains poorly understood. In this study, we explore effects of radiation on CAF-derived immunoregulatory signals to the TME. Methods: Primary CAF cultures were established from freshly collected human NSCLC lung tumors. CAFs were exposed to single-high or fractionated radiation regimens (1x18Gy or 3x6Gy), and the expression of different immunoregulatory cell-associated and secreted signaling molecules was analyzed 48h and 6 days after initiation of treatment. Analyses included quantitative measurements of released damage-associated molecular patterns (DAMPs), interferon (IFN) type I responses, expression of immune regulatory receptors, and secretion of soluble cytokines, chemokines, and growth factors. CAFs are able to survive ablative radiation regimens, however they enter into a stage of premature cell senescence. Results: Our data show that CAFs avoid apoptosis and do not contribute by release of DAMPs or IFN-I secretion to radiation-mediated tumor immunoregulation. Furthermore, the secretion of relevant immunoregulatory cytokines and growth factors including TGF-ß, IL-6, IL-10, TNFα, IL-1ß, VEGF, CXCL12, and CXCL10 remain comparable between non-irradiated and radiation-induced senescent CAFs. Importantly, radiation exposure modifies the cell surface expression of some key immunoregulatory receptors, including upregulation of CD73 and CD276. Discussion: Our data suggest that CAFs do not participate in the release of danger signals or IFN-I secretion following radiotherapy. The immune phenotype of CAFs and radiation-induced senescent CAFs is similar, however, the observed elevation of some cell surface immunological receptors on irradiated CAFs could contribute to the establishment of an enhanced immunosuppressive TME after radiotherapy.

Exploring the LET dependence of DNA DSB repair kinetics using the DR DNA database.

The repair of DNA double-strand breaks is a crucial yet delicate process which is affected by a multitude of factors. In this study, our goal is to analyse the influence of the linear energy transfer (LET) on the DNA repair kinetics. By utilizing the database of repair of DNA and aggregating the results of 84 experiments, we conduct various model fits to evaluate and compare different hypothesis regarding the effect of LET on the rejoining of DNA ends. Despite the considerable research efforts dedicated to this topic over the past decades, our findings underscore the complexity of the relationship between LET and DNA repair kinetics. This study leverages big data analysis to capture overall trends that single experimental studies might miss, providing a valuable model for understanding how radiation quality impacts DNA damage and subsequent biological effects. Our results highlight the gaps in our current understanding, emphasizing the pressing need for further investigation into this phenomenon.

Phytosanitary irradiation as an effective treatment for Drosophila suzukii.

Drosophila suzukii is a pest native to Southeast Asia that causes significant economic losses to soft fruit crops. Phytosanitary irradiation is a promising treatment for D. suzukii hosts; yet an internationally recognized irradiation protocol is lacking. To fulfil specific requirements for proposing an irradiation treatment for D. suzukii, naturally infested blueberries and cherries containing a total of 37,489 late pupae were irradiated with a maximum absorbed dose of 80 Gy. Infested hosts containing a total of 9578 late pupae were considered unirradiated controls. Prevention of egg laying by females that emerged from treated pupae was considered the treatment endpoint. The fecundity and egg viability of females that emerged from treated pupae mated with their siblings were evaluated using blueberries. While females from unirradiated pupae laid a total of 43,142 eggs, no egg was laid by females that emerged from irradiated pupae. In addition, 1-day-old adults were irradiated with nominal doses of 20 and 72 Gy to evaluate whether egg laying could be prevented in flies emerging before the irradiation treatment. Females irradiated with 72 Gy laid eggs that did not hatch. Our findings suggest the minimum absorbed dose of 80 Gy as a phytosanitary irradiation treatment against D. suzukii and may support its inclusion as a treatment option in the annex of the International Standard for Phytosanitary Measures 28 (ISPM 28).

TolRad, a model for predicting radiation tolerance using Pfam annotations, identifies novel radiosensitive bacterial species from reference genomes and MAGs.

The trait of ionizing radiation (IR) tolerance is variable between bacterium, with species succumbing to acute doses as low as 60 Gy and extremophiles able to survive doses exceeding 10,000 Gy. While survival screens have identified multiple highly radioresistant bacteria, such systemic searches have not been conducted for IR-sensitive bacteria. The taxonomy-level diversity of IR sensitivity is poorly understood, as are genetic elements that influence IR sensitivity. Using the protein domain (Pfam) frequencies from 61 bacterial species with experimentally determined D10 values (the dose at which only 10% of the population survives), we trained TolRad, a random forest binary classifier, to distinguish between radiosensitive (D10 < 200 Gy) and radiation-tolerant (D10 > 200 Gy) bacteria. On untrained species, TolRad had an accuracy of 0.900. We applied TolRad to 152 UniProt-hosted bacterial proteomes associated with the human microbiome, including 37 strains from the ATCC Human Microbiome Collection, and classified 34 species as radiosensitive. Whereas IR-sensitive species (D10 < 200 Gy) in the training data set had been confined to the phylum Proteobacterium, this initial TolRad screen identified radiosensitive bacteria in two additional phyla. We experimentally validated the predicted radiosensitivity of a Bacteroidota species from the human microbiome. To demonstrate that TolRad can be applied to metagenome-assembled genomes (MAGs), we tested the accuracy of TolRad on Egg-NOG assembled proteomes (0.965) and partial proteomes. Finally, three collections of MAGs were screened using TolRad, identifying further phyla with radiosensitive species and suggesting that environmental conditions influence the abundance of radiosensitive bacteria. IMPORTANCE: Bacterial species have vast genetic diversity, allowing for life in extreme environments and the conduction of complex chemistry. The ability to harness the full potential of bacterial diversity is hampered by the lack of high-throughput experimental or bioinformatic methods for characterizing bacterial traits. Here, we present a computational model that uses de novo-generated genome annotations to classify a bacterium as tolerant of ionizing radiation (IR) or as radiosensitive. This model allows for rapid screening of bacterial communities for low-tolerance species that are of interest for both mechanistic studies into bacterial sensitivity to IR and biomarkers of IR exposure.

Role of autophagy in modulating tumor cell radiosensitivity: Exploring pharmacological interventions for glioblastoma multiforme treatment.

Autophagy is an innate cellular process characterized by self-digestion, wherein cells degrade or recycle aged proteins, misfolded proteins, and damaged organelles via lysosomal pathways. Its crucial role in maintaining cellular homeostasis, ensuring development and survival is well established. In the context of cancer therapy, autophagy's importance is firmly recognized, given its critical impact on treatment efficacy. Following radiotherapy, several factors can modulate autophagy including parameters related to radiation type and delivery methods. The concomitant use of chemotherapy with radiotherapy further influences autophagy, potentially either enhancing radiosensitivity or promoting radioresistance. This review article discusses some pharmacological agents and drugs capable of modulating autophagy levels in conjunction with radiation in tumor cells, with a focus on those identified as potential radiosensitizers in glioblastoma multiforme treatment.

Molecular biological mechanisms of radiotherapy-induced skin injury occurrence and treatment.

Radiotherapy-Induced Skin Injury (RISI) is radiation damage to normal skin tissue that primarily occurs during tumor Radiotherapy and occupational exposure. The risk of RISI is high due to the fact that the skin is not only the first body organ that ionizing radiation comes into contact with, but it is also highly sensitive to it, especially the basal cell layer and capillaries. Typical clinical manifestations of RISI include erythema, dry desquamation, moist desquamation, and ulcers, which have been established to significantly impact patient care and cancer treatment. Notably, our current understanding of RISI's pathological mechanisms and signaling pathways is inadequate, and no standard treatments have been established. Radiation-induced oxidative stress, inflammatory responses, fibrosis, apoptosis, and cellular senescence are among the known mechanisms that interact and promote disease progression. Additionally, radiation can damage all cellular components and induce genetic and epigenetic changes, which play a crucial role in the occurrence and progression of skin injury. A deeper understanding of these mechanisms and pathways is crucial for exploring the potential therapeutic targets for RISI. Therefore, in this review, we summarize the key mechanisms and potential treatment methods for RISI, offering a reference for future research and development of treatment strategies.

Single-cell RNA-Seq analysis of molecular changes during radiation-induced skin injury: the involvement of Nur77.

Introduction: Ionizing radiation has been widely used in industry, medicine, military and agriculture. Radiation-induced skin injury is a significant concern in the context of radiotherapy and accidental exposure to radiation. The molecular changes at the single-cell level and intercellular communications during radiation-induced skin injury are not well understood. Methods: This study aims to illustrate this information in a murine model and human skin samples from a radiation accident using single-cell RNA sequencing (scRNA-Seq). We further characterize the functional significance of key molecule, which may provide a potential therapeutic target. ScRNA-Seq was performed on skin samples from a nuclear accident patient and rats exposed to ionizing radiation. Bioinformatic tools were used to analyze the cellular heterogeneity and preferential mRNAs. Comparative analysis was performed to identify dysregulated pathways, regulators, and ligand-receptor interactions in fibroblasts. The function of key molecule was validated in skin cells and in three mouse models of radiation-induced skin injury. Results: 11 clusters in human skin and 13 clusters of cells in rat skin were depicted respectively. Exposure to ionizing radiation caused changes in the cellular population (upregulation of fibroblasts and endothelial cells, downregulation of keratinocytes). Fibroblasts and keratinocytes possessed the most interaction pairs with other cell lineages. Among the five DEGs common to human and rat skins, Nur77 was highly expressed in fibroblasts, which mediated radiosensitivity by cell apoptosis and modulated crosstalk between macrophages, keratinocytes and endothelial cells in radiation-induced skin injury. In animal models, Nur77 knock-out mice (Nur77 -/-) showed more severe injury after radiation exposure than wild-type counterparts in three models of radiation-induced skin injury with complex mechanisms. Conclusion: The study reveals a single-cell transcriptional framework during radiation-induced skin injury, which provides a useful resource to uncover key events in its progression. Nur77 is a novel target in radiation-induced skin injury, which provides a potential therapeutic strategy against this disease.

Ionizing radiation and skin cancer - a review of current evidence.

Cancer of the skin represents a challenge for radiological protection, as it is very common and involves the largest organ of the human body, which is exposed to environmental stress, including ionizing radiation. The most common subtypes, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) have very low mortality. Current consideration of skin cancer in radiological protection is mainly based on data from the 1990s, which indicate that BCC may be induced by ionizing radiation, SCC is only weakly associated with ionizing radiation, and malignant melanoma (MM) is not considered as ionizing radiation-induced. In a semi-systematic review of the evidence between 1990 and 2023, we snowballed 19 index articles. We identified 29 articles with information on a potential dose-response relationship between skin cancer and ionizing radiation exposure and assessed the evidence for a causal association. Exposure situations included a-bomb survivors, therapeutic and occupational exposure (airlines, nuclear and medical facilities) and residents exposed to radon. There is currently no epidemiological evidence that MM or SCC are caused by ionizing radiation. The only skin cancer type with evidence for a causal relationship is BCC, and evidence is limited to exposures above 0.5 Gy with a wide range of risk levels per dose. Thus, ionizing radiation-inducible skin cancer refers to BCC only and only at levels of exposure beyond those experienced by the vast majority of people exposed today.

Umbelliprenin improved anti-proliferative effects of ionizing radiation on adult T-cell leukemia/lymphoma cells via interaction with CDK6; an in vitro and in silico study.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy with poor survival rates. The efficacy of radiotherapy in ATL needs enhancement with radiosensitizing agents. This study investigated whether umbelliprenin (UMB) could improve the therapeutic effects of ionizing radiation (IR) in ATL cells. UMB, a naturally occurring prenylated coumarin, exhibits anticancer properties and has shown synergistic effects when combined with chemotherapeutic drugs. Despite this promising profile, there is a notable lack of research on its potential combinatorial effects with IR, particularly for ATL treatment. UMB was extracted from Ferula persica using thin layer chromatography. MT-2 cells were treated with UMB alone and in combination with various doses of IR, and cell proliferation was assessed via alamarBlue assay. Flow cytometry with annexin V and PI staining was conducted, and candidate gene expression was analyzed by qPCR. In silico analysis involved identifying pathogenic targets of ATL, constructing protein-protein interaction (PPI) networks, and evaluating CDK6 expression in MT-2 cells. Molecular docking was used to determine the interaction between UMB and CDK6. The alamarBlue assay and flow cytometry showed that pretreating ATL cells with UMB significantly (p < .0001) enhanced anti-proliferative effects of IR. The combination index indicated a synergistic effect between UMB and IR. qPCR revealed significant (p < .0001) downregulation of CD44, CDK6, c-MYC, and cFLIPL, and overexpression of cFLIPS. Computational analysis identified CDK6 as a hub gene in the PPI network, and CDK6 overexpression was confirmed in MT-2 cells. Molecular docking revealed a favorable binding interaction between UMB and the ATP-binding site of CDK6, with a JAMDA score of -2.131, surpassing the control selonsertib. The current study provides evidence that UMB enhances the anti-proliferative effects of IR on ATL cells, and highlights the significance of targeting CDK6 in combinatorial approaches.

Radiation-Induced Intestinal Injury: Molecular Mechanisms and Therapeutic Status.

Radiation-induced intestinal injury is one of the most common intestinal complications caused by pelvic and abdominal tumor radiotherapy, severely impacting patients' quality of life. Ionizing radiation, while killing tumor cells, inevitably damages healthy tissue. Radiation-induced enteropathy results from radiation therapy-induced intestinal tissue damage and inflammatory responses. This damage involves various complex molecular mechanisms, including cell apoptosis, oxidative stress, release of inflammatory mediators, disruption of immune responses, and imbalance of intestinal microbiota. A thorough understanding of these molecular mechanisms is crucial for developing effective prevention and treatment strategies.

N-formylmethionine-leucyl-phenylalanine protects against irradiation-induced damage to hematopoiesis and intestines.

BACKGROUND: Ionizing radiation (IR), including radiotherapy, can exert lasting harm on living organisms. While liposaccharide (LPS) offers resistance to radiation damage, it also induces toxic responses. Thankfully, an LPS analogue called N-formylmethionine-leucyl-phenylalanine (fMLP) holds the potential to mitigate this toxicity, offering hope for radiation protection. METHODS: Survival of C57BL/6 mice exposed to IR after administration with fMLP/LPS/WR-2721 or saline was recorded. Cell viability and apoptosis assay of bone marrow (BMC), spleen and small intestinal epithelial (HIECs) cells were tested by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Tissue damage was evaluated by Hematoxilin and Eosin (H&E), Ki-67, and TUNEL staining. RNA sequencing was performed to reveal potential mechanisms of fMLP-mediated radiation protection. Flow cytometry and western blot were performed to verify the radiation protection mechanism of fMLP on the cell cycle. RESULTS: The survival rates of C57BL/6 mice exposed to ionizing radiation after administering fMLP increased. fMLP demonstrated low toxicity in vitro and in vivo, maintaining cell viability and mitigating radiation-induced apoptosis. Moreover, it protected against tissue damage in the hematopoietic and intestinal system. RNA sequencing shed light on fMLP's potential mechanism, suggesting its role in modulating innate immunity and cell cycling. This was evidenced by its ability to reverse radiation-induced G2/M phase arrests in HIECs. CONCLUSION: fMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR's detrimental effects.

Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography - a prospective single-center study.

BACKGROUND: Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of in vivo radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies. OBJECTIVE: Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography. MATERIALS AND METHODS: Prospective single-site study of 27 children. Blood collected pre and post neuroangiography, from which PBMC were isolated and assayed for biomarkers of mitochondrial stress (mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial DNA (mtDNA)) and DNA damage (γH2AX). Dose response of biomarkers vs. radiation dose was analyzed using linear regressions. The cohort was divided into higher (HD) and lower dose (LD) groups and analyzed using linear mixed models and compared using Welch's t-tests. RESULTS: No biomarker exhibited a dose-dependent response following radiation (γH2AX: R2 = 0.0012, P = 0.86; MMP: R2 = 0.016, P = 0.53; mtDNA: R2 = 0.10, P = 0.11; ROS: R2 = 0.0023, P = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, P = 0.92; HD: -7.5 ± 6.3 AU, P = 0.24; ROS: LD: 1.3 ± 2.8, P = 0.64; HD: -3.6 ± 3.0 AU, P = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, P = 0.0014) and mtDNA (-1.1 ± 0.4 AU, P = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, P = 0.090; mtDNA: 0.2 ± 0.4, P = 0.65). CONCLUSIONS: Biomarkers of mitochondrial stress in PBMC were identified during pediatric neuroangiography and warrant further investigation for radiation biodosimetry. However, isolating radiation-specific effects from those of procedural stress and general anesthesia requires further investigation.

Differential biological effect of low doses of ionizing radiation depending on the radiosensitivity in a cell line model.

PURPOSE: Exposure to low doses (LD) of ionizing radiation (IR), such as the ones employed in computed tomography (CT) examination, can be associated with cancer risk. However, cancer development could depend on individual radiosensitivity. In the present study, we evaluated the differences in the response to a CT-scan radiation dose of 20 mGy in two lymphoblastoid cell lines with different radiosensitivity. MATERIALS AND METHODS: Several parameters were studied: gene expression, DNA damage, and its repair, as well as cell viability, proliferation, and death. Results were compared with those after a medium dose of 500 mGy. RESULTS: After 20 mGy of IR, the radiosensitive (RS) cell line showed an increase in DNA damage, and higher cell proliferation and apoptosis, whereas the radioresistant (RR) cell line was insensitive to this LD. Interestingly, the RR cell line showed a higher expression of an antioxidant gene, which could be used by the cells as a protective mechanism. After a dose of 500 mGy, both cell lines were affected by IR but with significant differences. The RS cells presented an increase in DNA damage and apoptosis, but a decrease in cell proliferation and cell viability, as well as less antioxidant response. CONCLUSIONS: A differential biological effect was observed between two cell lines with different radiosensitivity, and these differences are especially interesting after a CT scan dose. If this is confirmed by further studies, one could think that individuals with radiosensitivity-related genetic variants may be more vulnerable to long-term effects of IR, potentially increasing cancer risk after LD exposure.

Radiation Dose Units: How We Got Here, Do They Serve the Purposes They are Intended to?

The current radiation dose estimates used in medical imaging, radiation oncology or environmental assessments are not entirely accurate from a fundamental physics perspective, let alone for biological consequences. The "one cloth fits all" approach of radiation-matter interactions cannot assess the effects of interactions of the same species of radiation of different energies on the same isotope of an element. Preliminary steps to set the radiation dosimetry in the right direction are suggested.

Long-term biological effects after acute 131I-administration of two rat models (with and without thyroid).

PURPOSE: Radioiodine-131 (RAI or iodine-131) is one of the most frequently used radionuclides for diagnosis and therapy of thyroid diseases (90% of all therapies in nuclear medicine). In order to optimize the patient protection, it is important to evaluate the long-term biological effects of RAI therapy on non-target organs. MATERIALS AND METHODS: An experimental animal model has been adopted, it consists on miming RAI therapy. An activity of RAI has been administrated in two models of Wistar rats: the first model with an intact thyroid gland (Thy + model), and the second one was thyroidectomized (Thy- model). For each model, 6 rats were orally contaminated with a solution 18.5 ± 1MBq of [131I]NaI and 6 others rats were used as controls. The 24 rats have been placed in individual cages for a period of 08 months then they were euthanized. The blood was collected by cardiac puncture and all organs were immediately removed. A fraction of thyroid, liver, kidneys and testicles was put in vials containing formaldehyde (10%) for histological investigation. RESULTS: Histological observations show some liver disorders more accentuated in the case of the Thy- model, the appearance of kidney tissue effects (hemosiderin deposits, fibrosis and glomerular necrosis) for both models and an absence of any anomaly for the testicles slides. The disturbance of blood parameters specific to each organ has been revealed. CONCLUSIONS: Long-term biological effect of 131I-administration shows the appearance of various histological disorders confirmed by disturbances in hepatic and renal functions.