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Exposure to ionizing radiation, especially during childhood, is a well-established risk factor for thyroid cancer. Following the 1986 Chernobyl nuclear power plant accident the total number of cases of thyroid cancer registered between 1991 and 2015 in males and females who were less than 18 years old exceeded 19,000 (in Belarus and Ukraine, and in the most contaminated oblasts of the Russian Federation). However, as indicated by the United Nations Scientific Committee on the Effects of Atomic Radiation the fraction of the incidence of thyroid cancer attributable to radiation exposure among the non-evacuated residents of the contaminated regions of Belarus, Ukraine and Russia is of the order of 0.25. Apparently, the increased registration of thyroid neoplasms in the parts of these countries is a classical ‘screening effect’, i.e., massive diagnostic examinations of the risk-aware populations performed with modern eqipment resulting in detection of many occult neoplasms (incidentalomas). Moreover, one type of thyroid cancer previously called ‘encapsulated follicular variant of papillary thyroid carcinoma’ is non-invasive and instead of ‘carcinoma’ should now be recognized as ‘noninvasive follicular thyroid neoplasm with papillary-like nuclear features.’ Other potential causes of overdiagnosing of thyroid tumors include increase of the spontaneous incidence rate of this disease with age, iodine deficiency among children from Belarus, Russia and Ukraine, and/or consumption by these children of drinking water containing high levels of nitrates that likely coincides with the carcinogenic effect of radiation on the thyroid gland.

The Pediatric Emergency Care Applied Research Network rule helps emergency physicians identify very low-risk children with minor head injury who can forgo head computed tomography. This rule contributes to reducing lifetime risk of radiation-induced cancers while minimizing missing clinically important traumatic brain injury. However, in intermediate-risk children, decisions on whether to perform computed tomography remain at the emergency physicians' discretion. To reduce this gray zone, this review summarizes evidence for risk stratification of intermediate-risk children with minor head injury.

Background: The Mentha-Pulegium essential oil (MP-EO) contains different antioxidant compounds and reduces the indirect effects of dispersed ionizing radiation on biological systems. Objective: The current study aimed to assess a possible radio-protective effect of MP-EO on peripheral blood mononuclear cells (PBMCs).Material and Methods: In this experimental study, MP-EO was firstly prepared and PBMCs were then irradiated in various groups with doses of 25 and 200 cGy of X-rays in the presence of IC10 of MP-EO. After incubation times of 48h and 72h, the survival, apoptosis, and necrosis percentages of PBMCs were determined by MTT assay and flow cytometry analyses; the radio-protective effect of MP-EO was examined. Results: In the presence of 80 µg/ml (IC10) MP-EO, the mean survival percentage of irradiated PBMCs by radiation doses of 25 and 200 cGy was significantly increased after 48h of incubation compared with the control. At 72h of incubation, the mean survival percentage of irradiated PBMCs was significantly increased only at 25 cGy. The percentage of apoptosis and necrosis of PBMCs was significantly reduced in the presence of the MP-EO at both incubation times and radiation doses; therefore, the highest reduction was at 200 cGy and 48h incubation compared to the control. Conclusion: MP-EO as a natural, non-toxic, and cost-effective compound can exhibit a favorable in-vitro radio-protective effect by increasing the survival and decreasing the percentage of apoptosis and necrosis of irradiated PBMCs.

The purpose of this study was to evaluate the effect of a single dose of ionizing radiation (30 Gy) on the osseointegration of implants in the rabbit tibia. Twenty rabbits received two dental Morse-tapered junction implants and one implant in each tibia. The animals were randomly divided into two groups (n=10), non-irradiated (NoIr) and irradiated (Ir), wherein the Ir group received a single dose of 30 Gy radiation 2 weeks after implant installation. Microtomographic analyses (BV/TV) and histomorphometric assessments (BIC and BABT) were performed 4 weeks after implant installation. One-way ANOVA, Tukey's test, and Student's t-test (α=0.05) were used for data analysis. The results showed that BV/TV did not differ significantly between the Ir and NoIr groups (P = 0.071). In the histomorphometric analysis, neither BIC nor BABT showed significant differences between the NoIr and Ir groups (p>0.05). In conclusion, ionizing radiation in dental implants does not appear to interfere with osseointegration when installed prior to irradiation.

Charged particle radiation can, directly and indirectly, affect cells by breaking DNA strands. This effect includes DNA single-strand breaks (SSB) and DNA double-strand breaks (DSB), which may cause cell death and mitotic failure. Thus, using short-range charged particles such as Auger electrons (AEs) not only leads to the destruction of the target cell but also prevents the nearby healthy cells from exposing to ionizing radiation. In this study, two spherical cells (C and C 2 ) and their cell nucleus, both made of liquid water, were modeled. An atomic DNA model constructed in the Geant4-DNA Monte Carlo (MC) simulation toolkit was placed inside the nucleus of the C and C 2 cells. The number of direct and indirect SSB, DSB, and hybrid DSB (HDSB), caused by some of the most widely-used Auger electron-emitting (AEE) radionuclides, including 99m Tc, 111 In, 123 I, 125 I, and 201 Tl, distributed within different compartments of the C cell, was calculated in the C and C 2 cells, considering the distance between the surface of the two cells ranges from 0 to 5 μm. The present work aimed to investigate the biological effects of AEE radionuclides and their potential for cancer treatment through targeted radiation therapy. The results indicate the impact of 201 Tl > 125 I > 123 I > 111 In > 99m Tc on DNA damage when the target is C (first spherical cell). On the other hand, for C 2 at distances of 0 to 5 μm, the impact of 99m Tc > 123 I > 111 In > 201 Tl > 125 I on DNA damage is observed., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Research involving human and animal rights: This article does not contain any studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Ionizing radiation (IR) can cause severe dysfunction of hematopoietic stem cells (HSCs), leading to acute or prolonged myelosuppression. In recent years, physical exercise has been recognized as a healthy lifestyle as it can fight a variety of diseases. However, whether it provides protection against IR is not fully understood. In this study, we revealed that long-term moderate exercise mitigated IR-induced hematopoietic injury by generating carnosine from skeletal muscles. We found that exercised mice displayed reduced loss of HSC number and function after IR, accompanied by alleviated bone marrow damage. Interestingly, these effects were largely abrogated by specific deletion of carnosine synthase Carns1 in skeletal muscles. In contrast, carnosine treatment protected HSCs against IR-induced injury. Mechanistically, we demonstrated that exercise-generated carnosine was specifically transported to HSCs via Slc15a2 and then inhibited p53 transcriptional activity by directly interacting with its core DNA-binding domain, which led to downregulation of the p53 target genes p21 and Puma, thus promoting the proliferation and survival and inhibiting the senescence of irradiated HSCs. More importantly, a similar role of the carnosine/Slc15a2-p53 axis was observed in human cord blood-derived HSCs. Collectively, our data reveal that moderate exercise or carnosine supplementation may be potential antiradiation strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s).)

RAS-selective lethal small molecule 3 (RSL3) is a small-molecule compound that triggers ferroptosis by inactivating glutathione peroxidase 4. However, its effect on the radioresistance of glioma cells and the underlying mechanisms remains unclear. In this study, we found that RSL3 sensitized glioma cells to ionizing radiation (IR) and enhanced IR-induced DNA double-strand breaks (DSBs). Inhibition of ferroptosis pathways partly prevented the clonogenic death caused by the IR/RSL3 combination but did not alleviate the DNA DSBs, indicating that RSL3 promotes IR-induced DNA DSBs via a non-ferroptotic mechanism. We demonstrated that transglutaminase 2 (TGM2) plays a vital role in the radiosensitization effect of RSL3 on glioma cells. Treatment with RSL3 downregulated TGM2 in a dose-dependent manner. Overexpression of TGM2 not only alleviated DNA DSBs but also inhibited clonogenic death caused by the IR/RSL3 combination. Mechanistically, RSL3 triggered oxidative stress in glioma cells, which promoted the S-gluthathionylation of TGM2 via upregulation of glutathione S-transferase P1(GSTP1), culminating in the proteasomal degradation of TGM2. This process resulted in the suppression of DNA repair mechanisms by impeding the nuclear accumulation of TGM2 and disrupting the interaction between TGM2 and topoisomerase IIα after irradiation. We also found that RSL3 inhibited glioma cell epithelial-mesenchymal transition (EMT) in both IR-treated and non-IR-treated cells. Overexpression of TGM2 prevented, while knockdown of TGM2 aggravated the EMT inhibition caused by RSL3, indicating that RSL3 also sensitized glioma cells to IR by inhibiting EMT via a TGM2-dependent mechanism. Furthermore, in mice bearing human U87 tumor xenografts, RSL3 administration synergized with IR to inhibit tumor growth, accompanied by TGM2 inhibition, DNA DSBs, and EMT inhibition in tumor tissues. Taken together, we demonstrated that RSL3 sensitizes glioma cells to IR by suppressing TGM2-mediated DNA repair and EMT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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 Łódź 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):415-423., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder affecting multiple systems, such as skeletal, cardiovascular, and ocular systems. MFS is predominantly caused by mutations in the FBN1 gene, which encodes the fibrillin-1 protein, crucial for connective-tissue integrity. FBN1 mutations lead to defective fibrillin, resulting in structurally compromised connective tissues. Additionally, these mutations cause aberrant TGF-β expression, contributing to vascular issues and increased susceptibility to radiation-induced fibrosis. Studies about the potential radiosensitivity of MFS are rare and generally limited to case reports. Here, we aimed to investigate the radiation-induced ATM nucleo-shuttling (RIANS) model to explore the molecular and cellular radiation response in fibroblasts from MFS patients. The results showed that the MFS fibroblast cell lines tested are associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired recognition of DNA double-strand breaks (DSBs) caused by a diminished RIANS. The diminished RIANS is supported by the sequestration of ATM protein in the cytoplasm not only by mutated FBN1 protein but also by overexpressed TGF-β. This report is the first molecular and cellular characterization of the radiation response of MFS fibroblasts and highlights the importance of the FBN1-TGF-β complex after irradiation.

Objectives: Vascular and interventional radiology procedures are characterized by high exposure of personnel to ionizing radiation. This study assessed the exposure of medical personnel to ionizing radiation during vascular radiology and mechanical thrombectomy procedures., Material and Methods: During vascular radiology procedures, the exposure of 4 groups of workers participating in the procedures was analyzed, i.e., the main operating physician, an assistant physician, a sterile nurse, and a nurse. Measurements of exposure to ionizing radiation were performed using thermoluminescent dosimetry., Results: The registered effective dose during 1 treatment in individual groups is, respectively: mean (M) ± standard deviation (SD) 75±15 μSv, 24±5 μSv, 13±3 μSv, and 8±2 μSv. During mechanical thrombectomy, the operating physician receives an effective dose of M±SD 9±2 μSv. The equivalent doses for the lenses for the operating physician and the doctor assisting during vascular radiology procedures are M±SD 1419±285 μSv and 987±198 μSv, respectively, and for the hands, including the left and right hands, M±SD 4605±930 μSv, 1420±284 μSv, 1898±380 μSv, 1371±274 μSv., Conclusions: If the principles of optimizing radiological protection are not applied during vascular radiology procedures, the permissible dose limits and operational limits equivalent to doses to lenses and hands may be exceeded. Exposure during vascular radiology procedures is comparable to exposure during nuclear medicine procedures in terms of the use of glucose labeled with radioactive fluorine. Int J Occup Med Environ Health. 2024;37(4):403-10., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Public health and clinical medicine should identify and characterize modifiable risk factors for skin cancer in order to facilitate primary prevention. In existing literature, the impact of occupational exposure on skin cancer, including malignant melanoma and non-melanoma skin cancers, has been extensively studied. This review summarizes the available epidemiological evidence on the significance of occupational risk factors and occupations associated with a higher risk in skin cancer. The results of this review suggest that there is sufficient epidemiological evidence to support the relationship between the increased risk of non-melanoma skin cancers and occupational exposure to solar radiation, ultraviolet radiation, ionizing radiation, arsenic and its compounds, and mineral oils. Occupational exposure to pesticides and polychlorinated biphenyls appears to provide sufficient epidemiological evidence for melanoma, and a higher risk of melanoma has been reported among workers in petroleum refining and firefighters. This comprehensive analysis will establish a foundation for subsequent investigations and developing targeted interventions of focused preventive measures against skin cancer among the working population., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

In the treatment of industrial wastewater by electron beam technology, the flocculation process was frequently coupled with electron beam radiation to improve the water quality to meet the discharge standard. Iron-containing coagulant was widely used in the flocculation process. Therefore, this study investigated the impact of residual iron-containing coagulants on pollutant degradation by the ionizing radiation process. Results showed that the absorbed dose required for complete removal of 50 mg/L bisphenol A decreased from 5 kGy to 2.5 kGy in the presence of 100 μM typical iron coagulant (FeCl 3 ). BPA degradation efficiency increased with the increase of FeCl 3 dosage over a wide pH range (3.0-10.0), and the TOC removal efficiency increased from 20% to 45% with the addition of 300 μM Fe(III). The mechanistic investigation demonstrated that • OH was the primary reactive species responsible for BPA degradation. The residual iron coagulants (FeCl 3 ) significantly enhanced the degradation and mineralization efficiency. Under suitable pH conditions (3.0-6.0), the reducing reactive species (e aq ‒ and • H) could effectively reduce Fe(III) to Fe(II), which then reacted with H 2 O 2 , thus inducing in-situ Fenton reaction to generate more • OH, thus promoting the radiolysis degradation of micropollutants. This study explored the potential of using residual iron coagulants from the flocculation process to enhance the performance of electron beam technology for wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Intestinal stem cells (ISCs) are responsible for intestinal homeostasis and are important for the regeneration of damaged intestine. We established an ionizing radiation (IR)-induced intestinal injury model and observed that Gelsolin KO mice had increased radiosensitivity. The deletion of Gelsolin aggravated intestinal damage and reduced the number of ISCs after lethal IR. The intestinal organoid experiments showed that Gelsolin deletion inhibited ISCs function after IR. Notably, RNA sequencing and RT-PCR results showed IL-17 signaling pathway was down-regulated and Th17 cells differentiation was inhibited in Gelsolin KO mice. Moreover, recombinant IL-17 A ameliorated IR-induced intestinal injury and promoted ISCs regeneration. To figure out the role of Gelsolin in Th17 cells differentiation, flow cytometry was used and we found that Gelsolin targets Th17 cells functionality via the p-STAT3/RORγt axis. By establishing the co-culture system, we proved that Th17 cells promoted self-renewal and budding abilities in Gelsolin-deficient organoids. Finally, we found that Gelsolin was protective against DSS-induced colitis and that this protective effect was not specific or limited to the IR induced intestinal injury model. Based on these results, we proved Gelsolin maintained the regeneration of ISCs by sustaining Th17 cells functions via the p-STAT3/RORγt axis., (© 2024. The Author(s).)

This study aimed to evaluate the effects of different scaling protocols on the morphology and roughness of the root dentin substrate exposure to ionizing radiation. One hundred and thirty extracted bovine incisors were randomly divided into two groups (n=65): non-irradiated (NIR) and irradiated (IR). Each group was initially subdivided into three subgroups according to the type of non-surgical periodontal protocol: NIT: no instrumentation; HS: hand scaling with 15 apical-coronal instrument movements; US: ultrasonic scaling with 15 apical-coronal cycles. Subsequently, all samples were subjected to the prophylaxis protocol, being subdivided into the following groups: NIT/PP: prophylaxis with a fine prophylactic paste using a rubber cup for 15 seconds; HS/PP: Hand scaling followed by the prophylaxis protocol; US/PP: Ultrasonic scaling followed by the prophylaxis protocol. The roughness of the root dentin surface was measured with a profilometer (Ra/Rz - μm), and the morphology of the dentin surfaces was analyzed using scanning electron microscopy (SEM). The analyses were conducted before and after the prophylaxis protocol. In the absence of prophylaxis, the roughest surfaces were observed after ultrasonic instrumentation followed by hand instrumentation for both IR and NIR groups. No difference in Ra and RZ values between HS/PP and US/PP was observed for both substrates. For the IR group, the prophylaxis resulted in similar Ra and RZ values for both instrumentation groups in comparison to no instrumentation. Ordinal logistic regression showed that both HS and US resulted in higher scores than NIT, irrespective of IR presence. In conclusion, the IR showed a rougher root surface for both HS and US in comparison to NIR. However, the prophylaxis procedure significantly reduced the roughness of root surfaces after both instrumentation procedures.

Background: Radiotherapy is a treatment modality used for head and neck cancer patients. It has a negative influence on bonding strength of adhesives. Little information is available about the effect of radiotherapy on bonding strength of adhesives in primary teeth. Therefore, this in vitro study aimed to detect the best adhesive system and ideal time to apply restorations in primary irradiated teeth regarding adhesive shear bond strength., Methods: Dentin samples from primary teeth were randomly assigned to four groups based on restoration application time and radiation exposure, (G1: control, G2: preradiation, G3: 24 h postradiation, and G4: 6 months postradiation) with 20 samples per group. These groups were further divided into 2 subgroups according to the adhesive system used, with 10 samples per subgroup. (1) 3M™ Single Bond Universal Adhesive (SB), (2) 3M AdperSingle Bond 2 (AS). Samples were exposed to gamma radiation from a cobalt-60 machine. One shot of 60 Gy of radiation was delivered. Then samples were subjected to a shear bond strength test. The load was applied until failure and the maximum load was recorded. Numerical data are presented as mean and standard deviation values, then distributed according to Shapiro-Wilk test or Levene's test and analyzed via two-way ANOVA. The significance level was set at p < 0.05 for all tests. Statistical analysis was performed with R statistical analysis software version 4.4.1 for Windows (Team RC, R: A language and environment for statistical computing. R foundation for statistical computing, 2023)., Results: Compared with the AS subgroup, the SB subgroup presented significantly greater values (p < 0.001). For SB, there was no significant difference among the G1 and G4 groups (p > 0.001). However, there was a significant difference between G1, G2, and G3 (p < 0.001, P = 0.025, P = 0.265 ns respectively), and G3 presented the lowest values. For AS, there was no significant difference between groups G1 and G4 (p =  < 0.001). Compared with the other groups, G3 presented a significant difference (p = 0.265 ns) and the lowest results., Conclusion: Restorations performed 24 h after radiation had lower bond strength than those performed six months after radiation. Regardless of the adhesive system used, SB performed better than AS in terms of the shear bond strength., (© 2024. The Author(s).)

Radiation liver injury is a common complication of hepatocellular carcinoma radiotherapy. It is mainly caused by irreversible damage to the DNA of hepatocellular cells directly by radiation, which seriously interferes with metabolism and causes cell death. AdipoRon can maintain lipid metabolism and stabilize blood sugar by activating adiponectin receptor 1 (AdipoR1). However, the role of AdipoRon/AdipoR1 in the regulation of ionizing radiation (IR)-induced mitochondrial damage remains unclear. In this study, we aimed to elucidate the roles of AdipoRon/AdipoR1 in IR-induced mitochondrial damage in normal hepatocyte cells. We found that AdipoRon treatment rescued IR-induced liver damage in mice and mitochondrial damage in normal hepatocytes in vivo and in vitro. AdipoR1 deficiency exacerbated IR-induced oxidative stress, mitochondrial dynamics, and biogenesis disorder. Mechanistically, the absence of AdipoR1 inhibits the activity of adenosine monophosphate-activated protein kinase α (AMPKα), subsequently leading to disrupted mitochondrial dynamics by decreasing mitofusin (MFN) and increasing dynamin-related protein 1 (DRP1) protein expression. It also controls mitochondrial biogenesis by suppressing the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) and transcription factor A (TFAM) signaling pathway, ultimately resulting in impaired mitochondrial function. To sum up, AdipoRon/AdipoR1 maintain mitochondrial function by regulating mitochondrial dynamics and biogenesis through the AdipoR1-AMPKα signaling pathway. This study reveals the significant role of AdipoR1 in regulating IR-induced mitochondrial damage in hepatocytes and offers a novel approach to protecting against damage caused by IR.

This study focused on exploring the effect of peroxydisulfate (PDS) on the regulation of reactive species during water radiolysis process and its potential application for degrading organic pollutants. The results indicated that PDS was successfully activated by ionizing radiation for efficient removal of three typical phenolic compounds over a wide pH range (3.0∼12.0) at absorbed dose of 5 kGy. Chemical probe methods provided the evidence that the addition of PDS could introduce the sulfate radicals (SO 4 •- ) and enhance the production of hydroxyl radicals ( • OH). According to the quenching tests, • OH and SO 4 •- were the dominant reactive species responsible for the degradation of 4-NP, while hydrated electron (e aq - ) played a minor role. The regulatory effect of PDS on active species in the ionizing radiation process could divided by (i) PDS could be directly activated by ionizing radiation to produce • OH and SO 4 •- via energy transfer pathway; (ii) PDS could boost the conversion of e aq - to SO 4 •- via electron transfer pathway. Furthermore, we assessed the applicability of the IR and IR/PDS systems in treating mixed solutions containing various pollutants and actual coking wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5-2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8 + T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations., (© 2024. The Author(s).)

In response to DNA double-strand damage, ongoing transcription is inhibited to facilitate accurate DNA repair while transcriptional recovery occurs after DNA repair is complete. However, the mechanisms at play and the identity of the transcripts being regulated in this manner are unclear. In contrast to the situation following UV damage, we found that transcriptional recovery after ionizing radiation (IR) occurs in a manner independent of the HIRA histone chaperone. Sequencing of the nascent transcripts identified a programmed transcriptional response, where certain transcripts and pathways are rapidly downregulated after IR, while other transcripts and pathways are upregulated. Specifically, most of the loss of nascent transcripts occurring after IR is due to inhibition of transcriptional initiation of the highly transcribed histone genes and the rDNA. To identify factors responsible for transcriptional inhibition after IR in an unbiased manner, we performed a whole genome gRNA library CRISPR/Cas9 screen. Many of the top hits on our screen were factors required for protein neddylation. However, at short times after inhibition of neddylation, transcriptional inhibition still occurred after IR, even though neddylation was effectively inhibited. Persistent inhibition of neddylation blocked transcriptional inhibition after IR, and it also leads to cell cycle arrest. Indeed, we uncovered that many inhibitors and conditions that lead to cell cycle arrest in G 1 or G 2 phase also prevent transcriptional inhibition after IR. As such, it appears that transcriptional inhibition after IR occurs preferentially at highly expressed genes in cycling cells., Competing Interests: ZC, XW, XG, NA, KC, JT No competing interests declared, (© 2024, Chen, Wang et al.)

Background/objectives: This study investigates consumer perceptions and acceptance of ionizing radiation (IoR) as a perishable food stabilisation technology. Consumers' preferences influence the success of emerging food technologies. Therefore, a comprehensive understanding of consumers' behavioural responses and their development over time is essential., Methods: This research employs a mixed-methods approach, surveying 313 young adults in New Zealand on their views of both irradiated (IoR) and genetically modified (GM) highly perishable foods. This study explored both participants' attitudes towards these two technologies and also their willingness to consume these foods., Results: The qualitative research revealed a preponderance of "affective" associations over "cognitive" associations with regard to both IoR and GM technologies. The quantitative research indicated that where consumers were given time to reflect, evaluations of GM improved, while those of IoR did not ( p < 0.01). There was a gender divide, with females being more positively inclined towards GM and males towards IoR ( p < 0.01). Both technologies were significantly disfavoured compared to non-treated products ( p < 0.01). There was a significant discrimination when the two technologies were presented as concepts and as products. GM was more favourably received as a concept than as a product ( p < 0.01), while IoR was disfavoured in either form. The two food neophobia scales that were tested showed a divergence in performance, with the more affectively based scale showing a higher level of correlation with behaviour., Conclusions: This research reveals that a largely affective (visceral) distrust of both IoR and GM exists within this young food consumer sample. As it is affective in nature, this position will be very resistant to education efforts, particularly if they are "cognitively" based. However, a significant softening of these affective attitudes towards GM products indicates that such efforts may be effective, given time and investment.

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 D 10 values (the dose at which only 10% of the population survives), we trained TolRad, a random forest binary classifier, to distinguish between radiosensitive ( D 10 < 200 Gy) and radiation-tolerant ( D 10 > 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 ( D 10 < 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., Competing Interests: The authors declare no conflict of interest.

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., (© 2024. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background/Aim. Exposure of living organisms to γ-radiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total super-oxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy.

ABSTRACT BACKGROUND: The largest radiological accident to occur in any urban area happened in Goiânia, Brazil, in 1987. OBJECTIVE: To evaluate the association between breast cancer incidence and ionizing radiation levels. DESIGN AND SETTING: Ecological study among residents of the city of Goiânia, Brazil. METHODS: The central region of Goiânia, with seven major sources of contamination from cesium-137, was defined as the study area. The addresses of women diagnosed with breast cancer were identified between 2001 and 2010. The data were geographically referenced and, using census data, the annual averages of crude incidence rates were estimated. The existence of clusters of new cases was ascertained by means of the Moran index. Correlations of radiometric measurements with the incidence were assessed using unconditional linear regression. RESULTS: A total of 4,105 new cases were identified, of which 2,233 were in the study area, and of these, 1,286 (57.59%) were georeferenced. The gross rates of total and referenced cases were 102.91 and 71.86/100,000 women, respectively. These were close to the average for Brazilian state capitals, which is 79.37/100,000 women. The cluster analysis showed slight correlations in three small sets of census tracts, but these were far from the sources of contamination. The scatter plot of points and the R2 value close to zero indicated that there was no association between the variables. CONCLUSION: This study reinforces the hypothesis that the ionizing radiation levels to which women living in Goiânia are now exposed to are not associated with the onset of new cases of breast cancer.

Background: Ionizing radiation is present in all environment of the Earth’s surface, beneath the Earth and in the atmosphere. Human beings are exposed to external radiation from their surroundings naturally and also to internal radiation from food, water and air they consume. Then, it is important to measure and develop knowledge about radiation. Objective: This study is designed to evaluate the risks of radiation outdoors and indoors and in hot spring in Gachine area of Bandar Abbas. Materials and Methods: The device used in this cross sectional study was environmental radiation surveymeter. Indoor gamma radiation in Gachine area was carried out inside 115 dwellings. Measurement for hot spring waters was carried out at one meter above water level. Dose rates were recorded for an hour. Results: Our results indicate the outdoor dose rate gamma radiation in Gachine area is higher than the global mean dose rate. Moreover, Gachine Bala has the highest outdoor gamma radiation (78.87 nGy/h) and Gachine Paien has the lowest gamma background radiation (71.62 nGy/h). Discussion: This study demonstrates that indoor mean dose rate of gamma radiation in this area is higher than the global mean dose rate. Estimated indoor mean dose rates were for Gachine Paien (110.58 nGy/h), Gachine Bala (111.83 nGy/h), Ship industry dwelling (109.30 nGy/h) and Jamal Ahmad (107.84 nGy/h). The highest dose rate above hot spring was obtained from Chostaneh (1320 nGy/h).

Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.

Objective: Radioactive intestinal injury is a common complication during radiotherapy of tumors. The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells., Methods: A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile acids were quantified using metabolomics analysis. IEC-6 cells, a small intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid (GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow cytometry. The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media. The expression levels of proteins associated with cell death were determined using Western blot., Results: After exposure to irradiation, the small intestine tissues of the rats showed typical radioactive intestinal injury. In addition, various bile acids showed fluctuation before and after irradiation. Among the bile acids, GUDCA increased significantly at 3 d after irradiation, but returned to the pre-irradiation level at 7 d after irradiation. Compared with the control group, after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after irradiation was significantly higher than that of the DMSO group ( P <0.05); the expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, were significantly lower than those in the control group ( P <0.05). After GUDCA treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group ( P <0.05). Compared with the DMSO control group, the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 6 Gy ( P <0.05). D 0 , or the mean lethal dose, of the GUDCA group was 6.374, while that of the DMSO group was 4.572. Compared with the DMSO control group, the D 0 value of the GUDCA treatment group increased, and the sensitization enhancement ratio (SER) was 0.717., Conclusion: After exposing the abdomen of rats to irradiation, the intestinal bile acid metabolism of the rats will change significantly, and GUDCA can produce radioprotective effects on intestinal cells to a certain extent., Competing Interests: 利益冲突　本文作者张舒羽是本刊编委会编委。该文在编辑评审过程中所有流程严格按照期刊政策进行，且未经其本人经手处理。除此之外，所有作者声明不存在利益冲突。, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with the TOPAS-nBio extension, capable of handling the track-structure simulation and subsequent chemistry, and CompuCell3D, an agent-based model simulator for biological and environmental behavior of a population of cells. We verified the implementation by simulating the experimental conditions for a clonogenic survival assay of a 2-D PC-3 cell culture model (10 cells in 10,000 µm 2 ) irradiated by MV X-rays at several absorbed dose values from 0-8 Gy. The simulation considered cell growth and division, irradiation, DSB induction, DNA repair, and cellular response. The survival was obtained by counting the number of colonies, defined as a surviving primary (or seeded) cell with progeny, at 2.7 simulated days after irradiation. DNA repair was simulated with an MC implementation of the two-lesion kinetic model and the cell response with a p53 protein-pulse model. The simulated survival curve followed the theoretical linear-quadratic response with dose. The fitted coefficients α = 0.280 ± 0.025/Gy and β = 0.042 ± 0.006/Gy 2 agreed with published experimental data within two standard deviations. TOPAS-Tissue extends previous works by simulating in an end-to-end way the effects of radiation in a cell population, from irradiation and DNA damage leading to the cell fate. In conclusion, TOPAS-Tissue offers an extensible all-in-one simulation framework that successfully couples Compucell3D and TOPAS for multiscale simulation of the biological response to radiation.

DNA data storage is a potential alternative to magnetic tape for archival storage purposes, promising substantial gains in information density. Critical to the success of DNA as a storage media is an understanding of the role of environmental factors on the longevity of the stored information. In this paper, we evaluate the effect of exposure to ionizing particle radiation, a cause of data loss in traditional magnetic media, on the longevity of data in DNA data storage pools. We develop a mass action kinetics model to estimate the rate of damage accumulation in DNA strands due to neutron interactions with both nucleotides and residual water molecules, then utilize the model to evaluate the effect several design parameters of a typical DNA data storage scheme have on expected data longevity. Finally, we experimentally validate our model by exposing dried DNA samples to different levels of neutron irradiation and analyzing the resulting error profile. Our results show that particle radiation is not a significant contributor to data loss in DNA data storage pools under typical storage conditions., (© 2024. The Author(s).)

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

Humans live in an environment in which they are constantly exposed to meagre dose rates of radiation [...].

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., (© 2024. The Author(s).)

Objectives: During computed tomography (CT), a large amount of ionizing radiation is emitted to ensure high quality of the obtained radiological image. This study measured the dose distribution around the CT scanner and the exposure of people staying near the CT scanner during the examination., Material and Methods: The measurements used an anthropomorphic phantom to assess human exposure to ionizing radiation. The probability of inducing leukemia and other cancers as a result of absorbing doses recorded around the CT device was also calculated., Results: The highest exposure to scattered radiation in the proximity of the CT scanner is recorded at the gantry of the tomograph, i.e., 55.7 μGy, and the lowest, below lower detection limit of 6 μGy at the end of the diagnostic table. The whole-body detector placed on the anthropomorphic phantom located at the diagnostic table right next to the CT gantry recorded 59.5 μSv and at the end of the table 1.5 μSv. The average doses to the lenses in these locations were: 32.1 μSv and 2.9 μSv, respectively., Conclusions: The probability of induction of leukemia or other types of cancer is low, but the need for people to stay in the examination room during a CT examination should be limited to the necessary minimum. Int J Occup Med Environ Health. 2024;37(3):326-34., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

DNA damage has been implicated in the stimulation of the type 1 interferon (T1IFN) response. Here, we show that downregulation of the DNA repair protein, polynucleotide kinase/phosphatase (PNKP), in a variety of cell lines causes robust phosphorylation of STAT1, upregulation of interferon-stimulated genes and persistent accumulation of cytosolic DNA, all of which are indicators for the activation of the T1IFN response. Furthermore, this did not require damage induction by ionizing radiation. Instead, our data revealed that production of reactive oxygen species (ROS) synergises with PNKP loss to potentiate the T1IFN response, and that loss of PNKP significantly compromises mitochondrial DNA (mtDNA) integrity. Depletion of mtDNA or treatment of PNKP-depleted cells with ROS scavengers abrogated the T1IFN response, implicating mtDNA as a significant source of the cytosolic DNA required to potentiate the T1IFN response. The STING signalling pathway is responsible for the observed increase in the pro-inflammatory gene signature in PNKP-depleted cells. While the response was dependent on ZBP1, cGAS only contributed to the response in some cell lines. Our data have implications for cancer therapy, since PNKP inhibitors would have the potential to stimulate the immune response, and also to the neurological disorders associated with PNKP mutation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background/aims: One of the treatments for breast cancer is surgical resection of the tumour and prevention of recurrence with postoperative radiotherapy. Unfortunately, radiotherapy is not always effective enough due to the low sensitivity of cancer cells to ionising radiation. This study aimed to evaluate the radiosensitising properties of resveratrol, piceatannol and polydatin on breast cancer cells, which differ in the presence of hormonal receptors on their surface., Methods: The experimental part was carried out on triple-negative breast cancer cells (HCC38) and hormone-dependent cells (MCF7). The study assessed the level of cell death, changes in the expression of genes (BAX, BCL-2) and proteins related to the apoptosis process (CASPASE 3, 8 and P53), changes in the expression of antioxidant enzymes (CATALASE, SOD, GPx1/2) and NRF-2. Additionally, the expression level of RAD51 protein and histone H2AX, which are involved in DNA repair processes, was assessed. Statistical significance was evaluated by a two-way analysis of variance (ANOVA) followed by Tukey's post hoc test (p < 0.05)., Results: Ionising radiation in combination with resveratrol or piceatannol activates the apoptosis process by internal and external pathways. Greater sensitivity of MCF7 cells compared to HCC38 cells to ionising radiation in combination with resveratrol is associated with a weaker antioxidant response of cells and reduced intensity of DNA damage repair. DNA repair induced by ionising radiation occurs more effectively in HCC38 cells than in MCF7 cells., Conclusion: Resveratrol has the highest radiosensitising potential among the tested stilbene for cells of both lines. The effectiveness of ionizing radiation in combination with resveratrol (to a lesser extent with piceatannol) is more significant in MCF7 than in HCC38 cells., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

The one-carbon metabolism enzyme bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is among the most overexpressed proteins across tumors and is widely recognized as a promising anticancer target. While MTHFD2 is mainly described as a mitochondrial protein, a new nuclear function is emerging. Here, we observe that nuclear MTHFD2 protein levels and association with chromatin increase following ionizing radiation (IR) in an ataxia telangiectasia mutated (ATM)- and DNA-dependent protein kinase (DNA-PK)-dependent manner. Furthermore, repair of IR-induced DNA double-strand breaks (DSBs) is delayed upon MTHFD2 knockdown, suggesting a role for MTHFD2 in DSB repair. In support of this, we observe impaired recruitment of replication protein A (RPA), reduced resection, decreased IR-induced DNA repair protein RAD51 homolog 1 (RAD51) levels and impaired homologous recombination (HR) activity in MTHFD2-depleted cells following IR. In conclusion, we identify a key role for MTHFD2 in HR repair and describe an interdependency between MTHFD2 and HR proficiency that could potentially be exploited for cancer therapy., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Ionizing radiation (IR) poses a significant threat to both the natural environment and biological health. Exposure to specific doses of ionizing radiation early in an organism's development can lead to developmental toxicity, particularly neurotoxicity. Through experimentation with Xenopus laevis (X. laevis), we examined the effects of radiation on early developmental stage. Our findings revealed that radiation led to developmental abnormalities and mortality in X. laevis embryos in a dose-dependent manner, disrupting redox homeostasis and inducing cell apoptosis. Additionally, radiation caused neurotoxic effects, resulting in abnormal behavior and neuron damage in the embryos. Further investigation into the underlying mechanisms of radiation-induced neurotoxicity indicated the potential involvement of the neuroactive ligand-receptor interaction pathway, which was supported by RNA-Seq analysis. Validation of gene expression associated with this pathway and analysis of neurotransmitter levels confirmed our hypothesis. In addition, we further validated the important role of this signaling pathway in radiation-induced neurotoxicity through edaravone rescue experiments. This research establishes a valuable model for radiation damage studying and provides some insight into radiation-induced neurotoxicity mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

DNA double strand breaks (DSBs) are critical for the efficacy of radiotherapy as they lead to cell death if not repaired. DSBs caused by ionizing radiation (IR) initiate histone modifications and accumulate DNA repair proteins, including 53BP1, which forms distinct foci at damage sites and serves as a marker for DSBs. DSB repair primarily occurs through Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). NHEJ directly ligates DNA ends, employing proteins such as DNA-PK cs , while HR, involving proteins such as Rad54, uses a sister chromatid template for accurate repair and functions in the S and G2 phases of the cell cycle. Both pathways are crucial, as illustrated by the IR sensitivity in cells lacking DNA-PK cs or Rad54. We generated mouse embryonic stem (mES) cells which are knockout (KO) for DNA-PK cs and Rad54 to explore the combined role of HR and NHEJ in DSB repair. We found that cells lacking both DNA-PK cs and Rad54 are hypersensitive to X-ray radiation, coinciding with impaired 53BP1 focus resolution and a more persistent G2 phase cell cycle block. Additionally, mES cells deficient in DNA-PK cs or both DNA-PK cs and Rad54 exhibit an increased nuclear size approximately 18-24 h post-irradiation. To further explore the role of Rad54 in the absence of DNA-PK cs , we generated DNA-PK cs KO mES cells expressing GFP-tagged wild-type (WT) or ATPase-defective Rad54 to track the Rad54 foci over time post-irradiation. Cells lacking DNA-PK cs and expressing ATPase-defective Rad54 exhibited a similar phenotypic response to IR as those lacking both DNA-PK cs and Rad54. Despite a strong G2 phase arrest, live-cell imaging showed these cells eventually progress through mitosis, forming micronuclei. Additionally, mES cells lacking DNA-PK cs showed increased Rad54 foci over time post-irradiation, indicating an enhanced reliance on HR for DSB repair without DNA-PK cs . Our findings underscore the essential roles of HR and NHEJ in maintaining genomic stability post-IR in mES cells. The interplay between these pathways is crucial for effective DSB repair and cell cycle progression, highlighting potential targets for enhancing radiotherapy outcomes.

Radiation therapy continues to be the cornerstone treatment for malignant brain tumors, the majority of which express wild-type p53. Therefore, the identification of drugs that promote the ionizing radiation (IR)-induced activation of p53 is expected to increase the efficacy of radiation therapy for these tumors. The growth inhibitory effects of CEP-1347, a known inhibitor of MDM4 expression, on malignant brain tumor cell lines expressing wild-type p53 were examined, alone or in combination with IR, by dye exclusion and/or colony formation assays. The effects of CEP-1347 on the p53 pathway, alone or in combination with IR, were examined by RT-PCR and Western blot analyses. The combination of CEP-1347 and IR activated p53 in malignant brain tumor cells and inhibited their growth more effectively than either alone. Mechanistically, CEP-1347 and IR each reduced MDM4 expression, while their combination did not result in further decreases. CEP-1347 promoted IR-induced Chk2 phosphorylation and increased p53 expression in concert with IR in a Chk2-dependent manner. The present results show, for the first time, that CEP-1347 is capable of promoting Chk2-mediated p53 activation by IR in addition to inhibiting the expression of MDM4 and, thus, CEP-1347 has potential as a radiosensitizer for malignant brain tumors expressing wild-type p53.

Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells, and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.

In major radiological events, rapid assays to detect ionizing radiation exposure are crucial for effective medical interventions. The purpose of these assays is twofold: to categorize affected individuals into groups for initial treatments, and to provide definitive dose estimates for continued care and epidemiology. However, existing high-throughput cytogenetic biodosimetry assays take about 3 days to yield results, which delays critical interventions. We have developed a multiwell-based variant of the chemical-induced G0-phase Premature Chromosome Condensation Assay that delivers same-day results. Our findings revealed that using a concentration of phosphatase inhibitor lower than recommended significantly increases the yield of cells with highly condensed chromosomes. These chromosomes exhibited increased fragmentation in a dose-dependent manner, enabling to quantify radiation damage using a custom Deep Learning algorithm. This algorithm demonstrated reasonable performance in categorizing doses into distinct treatment groups (84% and 80% accuracy for three and four iso-treatment dose bins, respectively) and showed reliability in determining the actual doses received (correlation coefficient of 0.879). This method is amendable to full automation and has the potential to address the need for same-day, high-throughput cytogenetic test for both dose categorization and dose reconstruction in large-scale radiation emergencies., (© 2024. The Author(s).)

In the last decade, geopolitical instability across the globe has increased the risk of a large-scale radiological event, when radiation biomarkers would be needed for an effective triage of an irradiated population. Ionizing radiation elicits a complex response in the proteome, genome, and metabolome and hence can be leveraged as rapid and sensitive indicators of irradiation-induced damage. We analyzed the plasma of total-body irradiated (TBI) leukemia patients (n = 24) and nonhuman primates (NHPs; n = 10) before and 24 h after irradiation, and we performed a global metabolomic study aiming to provide plasma metabolites as candidate radiation biomarkers for biological dosimetry. Peripheral blood samples were collected according to the appropriate ethical approvals, and metabolites were extracted and analyzed by liquid chromatography mass spectrometry. We identified an array of metabolites significantly altered by irradiation, including bilirubin, cholesterol, and 18-hydroxycorticosterone, which were detected in leukemia patients and NHPs. Pathway analysis showed overlapping perturbations in steroidogenesis, porphyrin metabolism, and steroid hormone biosynthesis and metabolism. Additionally, we observed dysregulation in bile acid biosynthesis and tyrosine metabolism in the TBI patient cohort. This investigation is, to our best knowledge, among the first to provide valuable insights into a comparison between human and NHP irradiation models. The findings from this study could be leveraged for translational biological dosimetry.

Ionizing radiation is a significant risk factor for cataracts, but the pathogenesis of radiation-induced cataracts remains incompletely understood. Ferroptosis, an iron-dependent form of programmed cell death discovered in recent years, has gained increasing attention for its role in various diseases. This article systematically reviews research progress on ionizing radiation, ferroptosis, age-related cataracts, and radiation-induced cataracts. It proposes the "ferroptosis hypothesis" for the pathogenesis of radiation-induced cataracts. Through ionization and oxidative stress effects, ionizing radiation leads to elevated free iron levels and exacerbated lipid peroxidation in lens cells, activating the ferroptosis pathway and resulting in lens opacity. The involvement of ferroptosis in the development of age-related cataracts suggests that it may also be an important pathogenic mechanism of radiation-induced cataracts. Targeting the ferroptosis pathway may be a novel strategy for preventing and treating radiation-induced cataracts. Furthermore, developing new ferroptosis-specific inhibitors with improved targeting and pharmacokinetic properties is also an essential direction for research on preventing and treating radiation-induced cataracts. The study of ferroptosis provides new insights into the mechanism and management of radiation-induced cataracts, potentially transforming radiation-induced cataracts from "inevitable" to "preventable and treatable.", Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Liang, Su, Xue and Zhan.)

Background: Radiation therapy is an effective local therapy for lung cancer. However, the interaction between genes and radiotherapy is multifaceted and intricate. Therefore, we explored the role of miR-93-5p in the proliferation, apoptosis, and migration abilities of A549 cells. Simultaneously, we also investigated the interactions between miR-93-5p and ionizing radiation (IR)., Methods: Cell Counting Kit-8, transwell, and apoptotic assay were performed to measure the proliferation, migration, and apoptosis abilities. The expression levels of miR-93-5p and its target gene in lung cancer were predicted using starBase v3.0. Then, data were validated using qPCR and western blot., Results: miR-93-5p significantly promoted the proliferation ( P < 0.01) and migration abilities ( P < 0.001) of A549 cells. Gasdermin E (GSDME) was identified to be a putative target of miR-93-5p and had a negative correlation with miR-93-5p ( P < 0.001). Overexpression of miR-93-5p significantly decreased GSDME in A549 ( P < 0.001). Interestingly, miR-93-5p decreased cell proliferation ( P < 0.01) and cell migration ( P < 0.01) and increased apoptosis ( P < 0.01) in A549 cells after exposure to IR., Conclusions: miR-93-5p is presumed to play an oncogenic role in lung cancer by enhancing A549 cell proliferation and migration. It can enhance the sensitivity of radiotherapy under IR conditions. We speculate that the miR-93-5p/GSDME pathway was inhibited, activating the GSDME-related pyroptosis pathway when the cells were exposed to IR. Therefore, miR-93-5p can overcome resistance to radiotherapy and improve the efficacy of radiotherapy., Competing Interests: The authors report no competing interests., (Copyright © 2024 Qingtao Ni et al.)

Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, to confer lung cancer cell resistance to ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair of IR-induced DNA double-strand breaks (DSBs) and PD-L1 loss downregulates non-homologous end joining (NHEJ) while overexpression of PD-L1 upregulates NHEJ. IR induces translocation of PD-L1 from the membrane into nucleus dependent on deglycosylation of PD-L1 at N219 and CMTM6 and leads to PD-L1 recruitment to DSBs foci. PD-L1 interacts with Ku in the nucleus and enhances Ku binding to DSB DNA. The interaction between the IgC domain of PD-L1 and the core domain of Ku is required for PD-L1 to accelerate NHEJ-mediated DSB repair and produce radioresistance. Thus, PD-L1, in addition to its immune inhibitory activity, acts as mechanistic driver for NHEJ-mediated DSB repair in cancer., (© 2024. The Author(s).)

Ubiquitination is a crucial posttranslational modification required for the proper repair of DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). DSBs are mainly repaired through homologous recombination (HR) when template DNA is present and nonhomologous end joining (NHEJ) in its absence. In addition, microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA) provide backup DSBs repair pathways. However, the mechanisms controlling their use remain poorly understood. By using a high-resolution CRISPR screen of the ubiquitin system after IR, we systematically uncover genes required for cell survival and elucidate a critical role of the E3 ubiquitin ligase SCF cyclin F in cell cycle-dependent DSB repair. We show that SCF cyclin F -mediated EXO1 degradation prevents DNA end resection in mitosis, allowing MMEJ to take place. Moreover, we identify a conserved cyclin F recognition motif, distinct from the one used by other cyclins, with broad implications in cyclin specificity for cell cycle control.

Breast cancer is the most diagnosed cancer in the world, and it is the primary cause of cancer death for women. The risk of breast cancer is increased by endogenous factors like hormones and exogenous factors like radiation exposure that causes damage to the mammary epithelial cells leading to an inflammatory response. Chronic inflammation creates a microenvironment composed of, among other factors, chemokines, and interleukins, which promote cancer. The gene expression of the interleukin 1 receptor type 1, the interleukin 1 receptor antagonist, the Interleukin 1 Receptor Accessory Protein, the interleukin 6 cytokine family signal transducer, the C-X-C motif chemokine ligand 3, the C-X-C motif chemokine ligand 5, and the C-X-C motif chemokine ligand 6 were analyzed in an estrogen and radiation experimental breast cancer model. Furthermore, the expression of these genes was correlated with immune cell infiltration, estrogen receptor expression, and their clinical relevance in breast cancer patients based on data provided by The Cancer Genome Atlas database online. Results given by the experimental breast cancer model showed that all genes related to inflammation respond to ionizing radiation alone or in combination with estrogen. On the other hand, the immune response depended on the breast cancer type and on the expression of the gene that encoded the estrogen receptor. Finally, the importance of the expression of these genes in breast cancer is such that high IL1R1 or IL1RAP is strongly related to patient survival. These findings may help to improve the understanding of the role of immune molecules in carcinogenesis and enhance therapeutic approaches.

The genome is constantly exposed to DNA damage from endogenous and exogenous sources. Fine modulation of DNA repair, chromatin remodeling, and transcription factors is necessary for protecting genome integrity, but the precise mechanisms are still largely unclear. We found that after ionizing radiation (IR), global trimethylation of histone H3 at lysine 4 (H3K4me3) was decreased at an early (5 min) post-IR phase but increased at an intermediate (180 min) post-IR phase in both human and mouse hematopoietic cells. We demonstrated that PTIP, a component of the MLL histone methyltransferase complex, is required for H3K4me3 upregulation in the intermediate post-IR phase and promotes cell cycle arrest by epigenetically inducing a cell cycle inhibitor, PRDM1. In addition, we found that PTIP expression is specifically downregulated in acute myeloid leukemia patients. These findings collectively suggest that the PTIP-PRDM1 axis plays an essential role in proper DNA damage response and its deregulation contributes to leukemogenesis., (© 2024. The Author(s).)