Low-dose Radiation Research Articles

Effects of low-dose rate radiation on immune and epigenetic regulation of the mouse testes.

This study investigated the effects of chronic low-dose-rate radiation exposure on gene expression related to immunological defense mechanisms and epigenetic regulation in the testis of male mice. The study found that radiation exposure (4.5 mGy/hr until 4000 mGy) led to a significant decrease in the expression of genes involved in epigenetic regulation and a significant increase in the expression of several genes linked to innate and acquired immunity, suggesting a noticeable effect on the immune response. In addition, there was a significant increase in the expression of SRY-box transcription factor 9, which plays a crucial role in testicular development, indicating a response to irradiation. These findings provide insights into the biological effects of chronic low-dose-rate radiation exposure on innate immunity and epigenetic regulation in the testis.

SOX combined with tislelizumab and low-dose radiation therapy for the neoadjuvant treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase Ib/II clinical trial

BackgroundRecently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.MethodsThis is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.DiscussionThis is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.Clinical trial registrationClinicalTrials.Gov, identifier NCT06266871.

Mitochondrial reactive oxygen species-mediated fibroblast activation has a role in tumor microenvironment formation in radiation carcinogenesis.

Cancer risks attributable to low-dose and low-dose-rate radiation are a serious concern for public health. Radiation risk assessment is based on lifespan studies among Hiroshima-Nagasaki A-bomb survivors; however, there are statistical limitations due to a small sample size for low-dose radiation. Therefore, basic biological studies are helpful in understanding the mechanism of radiation carcinogenesis. The detrimental effects of ionising radiation (IR) are caused by reactive oxygen species (ROS)-mediated oxidative DNA damage. IR-induced delayed ROS are produced in the electron transport chain reaction of the mitochondrial complex. Thus, mitochondria are a source of ROS and a primary target for ROS attacks. Consequently, mitochondrial dysfunction is thought to be a key event in the metabolic changes of cancer cells and is important in radiation-induced carcinogenesis. In this paper, we present recent findings on radiation carcinogenesis effect assessment, focusing on mitochondrial function as stress sensors.

DNAR-03. ONCOMAGNETIC TREATMENT KILLS GLIOMA CELLS BY INHIBITING MITOCHONDRIAL ELECTRON TRANSPORT AND BY INDUCING OXIDATIVE STRESS AND DNA DAMAGE

Abstract A new noninvasive cancer therapeutic device developed in our laboratory called the Oncomagnetic device involves repeated stimulation with oscillating magnetic fields (sOMF) produced by spinning permanent magnets. It is technologically and mechanistically distinct from the Optune® device approved by the FDA and provides a novel approach for CNS tumor treatment. In 7 end-stage GBM patients, this device reversed the progression of recurrent tumors causing >30% reduction in their contrast-enhanced volumes within 4 – 8 weeks of treatment. Immune-competent mice with implanted mouse glioma cells in their brains also showed marked reduction in tumor size, increased survival (p< 0.05, n = 9) and greater DNA damage (γ-H2AX foci) in implanted tumor after sOMF treatment. Normal mice exposed to sOMF for 4 months had no adverse effects on the brain and other organs. In-vitro, sOMF inhibited mitochondrial ETC complex-I and markedly increased reactive oxygen species (ROS) levels in GBM cells. Detection of γ-H2AX and 53BP1 foci showed that sOMF caused significant DNA damage in GBM cells and diffuse intrinsic pontine glioma (DIPG) cells but not in normal astroglial SVGp12 cells. GBM cells exposed to sOMF for 4 h caused cell cycle arrest in the G1 phase and 30% - 40% loss of surviving colonies detected by clonogenic cell survival assay, while normal SVGp12 cells were not affected. This loss of survival in GBM cells was rescued by the antioxidant Trolox. These results indicate that sOMF stimulation has high anticancer potency comparable to low dose radiation therapy at the cellular level with an underlying mechanism of action that is substantially different from that proposed for Optune® TTF.

Development of an Anthracene-Coated SMF-MMF-SMF Sensor for Low-Dose UV Radiation Detection and Dosimetry

Development of an Anthracene-Coated SMF-MMF-SMF Sensor for Low-Dose UV Radiation Detection and Dosimetry

Feasibility of balloon rectal spacer implantation in HDR and LDR brachytherapy for prostate cancer treatment

PurposeThis study evaluates the use of a biodegradable balloon rectal spacer in two prostate cancer patients undergoing Low Dose Radiation (LDR) and salvage High Dose Radiation (HDR) brachytherapy. The spacer aims to reduce radiation dose to adjacent organs, particularly the rectum, in patients previously treated with radiation. MethodsThe balloon spacer was implanted transperineally under transrectal ultrasonography (TRUS) guidance in two patients. For the LDR case (73-year-old, intermediate-risk), the balloon was placed post-implant with 55 iodine-125 seeds delivering 145 Gy. For the HDR case (66-year-old, high-risk), the balloon was placed one week before treatment, which delivered 23 Gy in two weekly fractions using 16 channels. ResultsThe balloon provided a 14-15mm separation between rectum and prostate. In the LDR case, prostate D90 was 149.1Gy (102.83%), V100 was 91.95%, and rectum D30 was 23.93Gy (16.50%). For the HDR case, prostate D90 was 11.63Gy (105.79%), V100 was 93.63%, and rectum D0.5cc was 8.04Gy (73.15%). Both patients tolerated the treatment well, with no observed postoperative complications at 6-month follow-up. ConclusionsThe use of a rectal balloon spacer in both salvage HDR and LDR brachytherapy is feasible and safe, allowing for controlled placement and providing rectal protection from high radiation doses.

A Million Person Study Innovation: Evaluating Cognitive Impairment and other Morbidity Outcomes from Chronic Radiation Exposure Through Linkages with the Centers for Medicaid and Medicare Services Assessment and Claims Data.

The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects.

AOP report: Development of an adverse outcome pathway for deposition of energy leading to abnormal vascular remodeling.

Cardiovascular diseases (CVDs) are complex, encompassing many types of heart pathophysiologies and associated etiologies. Radiotherapy studieshave shown that fractionated radiation exposure at high doses (3-17 Gy) to the heart increases the incidence of CVD. However, the effects of low doses of radiation on the cardiovascular system or the effects from space travel, where radiation and microgravity are important contributors to damage, are not clearly understood. Herein, the adverse outcome pathway (AOP) framework was applied to develop an AOP to abnormal vascular remodeling from the deposition of energy. Following the creation of a preliminary pathway with the guidance of field experts and authoritative reviews, a scoping review was conducted that informed final key event (KE) selection and evaluation of the Bradford Hill criteria for the KE relationships (KERs). The AOP begins with a molecular initiating event of deposition of energy; ionization events increase oxidative stress, which when persistent concurrently causes the release of pro-inflammatory mediators, suppresses anti-inflammatory mechanisms and alters stress response signaling pathways. These KEs alter nitric oxide levels leading to endothelial dysfunction, and subsequent abnormal vascular remodeling (the adverse outcome). The work identifies evidence needed to strengthen understanding of the causal associations for the KERs, emphasizing where there are knowledge gaps and uncertainties in both qualitative and quantitative understanding. The AOP is anticipated to direct future research to better understand the effects of space on the human body and potentially develop countermeasures to better protect future space travelers.

The efect of low-dose gamma radiation on the development of plants from irradiated Pisum sativum sprouts in laboratory experiments

The problem of radiation exposure to organisms is relevant for areas where nuclear industry enterprises are located. Plant biotests are widely used for biotesting of anthropogenic factors affecting the environment, including radiation. The sensitivity of growth and cytogenetic parameters of the biotest based on Pisum sativum to the action of gamma irradiation n has been shown before, but only at high doses. The purpose of this work was to evaluate the influence of low-dose gamma irradiation on the development of Pisum sativum over 6-10 days after irradiating the sprouts. In the experiments, seeds of the Radomir sowing variety from the collection of the pea breeding laboratory of Krasnoyarsk Research Institute of Agriculture - Federal Research Centre Krasnoyarsk Scientific Center SB RAS were used. Pea sprouts were irradiated with a 137Cs source for 24 and 72 hours, with the absorbed dose being 20 and 62 mGy. After irradiation, the sprouts were grown in a climatic chamber on hydroponics for 10 days (240 hours). The control consisted of non-irradiated sprouts grown under identical conditions. The experiments for the first time provided reliable data on the negative effects of gamma irradiation (20 and 62 mGy) on the development of sowing peas 6-10 days after irradiation. A negative effect of gamma irradiation on the growth of the main and lateral roots of young plants was revealed. The experiments with irradiated pea sprouts confirmed the previously known fact that plant roots are more sensitive to irradiation compared to shoots. The pattern of change in the length of the main root of peas over time during germination at a dose of 20 mGy is described by a linear equation, while for a higher dose of irradiation, 62 mGy, the data can be approximated by a logarithmic equation with saturation. The different character of root length dependence on the time of cultivation after irradiation indicates a possible trend in plant growth under various doses of irradiation and cultivation times.

Effect of FBG Fiber Dosimeter Division in Sensing Capability for Low Radiation Doses

ر A fiber Bragg grating (FBG) as a dosimeter is developed in this simulation study (based on Optisystem 21 software) by dividing its region into five individual regions. The division includes the same properties for all regions, which is a standard SiO2 optical fiber material. In dosimeters, it is convenient to introduce dopants to increase the fiber sensitivity. The new design accepts dopants and can work without such a dopant. Measurements for sensing deflected signals from the FBG sensor confirmed increased sensitivity for low-rate radiation doses in comparison to one bulk region in a traditional fiber dosimeter. The sensitivity of this dosimeter is based on both the FWHM line shape function and the amplitude of the deflected signals. The FBG dosimeter sensor can respond to low-dose radiation in a noticeable manner according to the type of applied simulated effect. Dosimeter body division for multi-regions gives rise to sensitivity in comparison to the traditional bulk region. The measured FWHM from the line-shape function for overall observed signals fluctuates from 0.374 MHz under applied temperature, stress x, y, z, and strain to 0.358, 0.373, 0.3733, 0.368, and 0.3737 MHz, respectively. While this range follows different fitting functions: Sin, Exp.Decay, SinSqu., Exp.Decay3, and GaussAmpl. For last effects, according to measured effect. The same measurements were carried out for signal amplitude variation, with these effects giving a variety of relationships indicating their existing contribution. Results confirmed an efficient tool for use in sensing for low x-ray and gamma ray radiation dose applications versus traditional bulk FBG sensor type.

Risks of Circulatory Diseases among Korean Radiation Workers Exposed to Low-dose Radiation.

High-dose radiation has been widely recognized as a risk factor for circulatory diseases. There is increasing evidence for risk of circulatory diseases in response to low and moderate radiation doses in recent years, but the results are not always consistent. We aimed to evaluate the associations between low-dose radiation exposure (<0.1 Gy) and the incidence of circulatory disease in a large cohort of Korean radiation workers. We collected data from a cohort of 187,001 radiation workers monitored for personal radiation dose since 1984 and linked with the National Health Insurance Service data from 2002 to 2021. Excess relative risks (ERRs) per 100 mGy were calculated to quantify the radiation dose-response relationship. The mean duration of follow-up was 13.3 years. A total of 12,705 cases of cerebrovascular disease (CeVD) and 19,647 cases of ischemic heart disease (IHD) were diagnosed during the follow-up period (2002-2021). The average cumulative heart dose was 4.10 mGy, ranging from 0 to 992.62 mGy. The ERR per 100 mGy with 10-year lagged cumulative heart doses was estimated at -0.094 (95% CI -0.248, 0.070) for CeVD and -0.173 (95% CI -0.299, -0.041) for IHD. The ERRs were not significantly changed after adjusting for confounding factors such as smoking, income, blood pressure, body mass index, and blood glucose level. A linear quadratic model was found to provide a better fit for the ERR of CeVD and IHD than a linear model (P = 0.009 and 0.030, respectively). There were no statistically significant variations in ERR/100 mGy estimates for either CeVD or IHD in terms of sex, attained age, and duration of employment; however, heterogeneity in the ERR/100 mGy estimates for CeVD among occupations was observed (P = 0.001). Our study did not find conclusive evidence supporting the association between occupational low-dose radiation and an increased risk of circulatory diseases. The significant negative ERR estimates for IHD need further investigation with a more extended follow-up period.

Low-dose radiation research insights in experimental animals: A gateway to therapeutic implications

In recent years, a significant research effort has been underway to explore the effects of low-dose radiation (LDR). Animal models play a key role in various fields of research, including biomedicine, pharmaceutical, environmental, and behavioral studies. The use of animal models has been an invaluable tool in radiation research for understanding radiation biology, assessing radiation risks, and developing strategies for radiation protection and medical management. In the present review, the initial part focuses on the deleterious effects of high-dose radiation, and in correlation to that, in the later part of the review, the emphasis has been given to experimental approaches to explore the beneficial effects of LDR using animal models. This review could help explore the innovative approach for future research targeting the therapeutic role of LDR in various diseases, including depression, Cancer, Parkinson’s disease, and Alzheimer’s disease. Keywords: animal model, high dose radiation, low dose radiation, mice, rat.

Random Threshold Model: A Low-Dose Radiation-Induced Risk Assessment Approach Considering Individual Susceptibility to Cancer.

Objectives: The linear no-threshold (LNT) model, which has been used for radiation protection purposes, was developed based on the assumption that exposure to even a small amount of radiation may cause cancer. However, although it is known in carcinogenesis that there is variation in radiation sensitivity among individuals, the LNT model does not adequately consider radiosensitive subgroups. In this paper, we represent susceptibility to contract cancer by radiation exposure by means of the threshold of a dose-response function, introduce an assumption that the thresholds are random to represent the variation of the radiosensitivity among individuals in a susceptible subgroup. We propose a novel method, the random threshold (RT) model, for determining the safe dose limit for the subgroup to protect cancer-susceptible individuals from radiation exposure. Conclusion: The proposed method is illustrated by targeting ATM gene (a cancer-susceptible gene) mutation carriers as a radiosensitive subgroup. For cancer risk associated with low-dose radiation exposure, the contribution of radiosensitivity cannot be ignored, thus the RT model would be more suitable for risk protection for radiosensitive subgroups instead of the LNT model. We also notice that it could be widely applicable for risk protection of not only low-dose radiation but also environmental pollutants.

Effect of Radon Inhalation on Murine Brain Proteins: Investigation Using Proteomic and Multivariate Analyses.

Radon is a known risk factor for lung cancer; however, it can be used beneficially, such as in radon therapy. We have previously reported the enhancement of antioxidant effects associated with trace amounts of oxidative stress as one of the positive biological effects of radon inhalation. However, the biological effects of radon inhalation are incompletely understood, and more detailed and comprehensive studies are required. Although several studies have used proteomics to investigate the effects of radon inhalation on body proteins, none has focused on brain proteins. In this study, we evaluated the expression status of proteins in murine brains using proteomic and multivariate analyses to identify those whose expressions changed following two days of radon inhalation at a concentration of 1,500 Bq/m3. We found associations of radon inhalation with the expressions of seven proteins related to neurotransmission and heat shock. These proteins may be proposed as biomarkers indicative of radon inhalation. Although further studies are required to obtain the detailed biological significance of these protein alterations, this study contributes to the elucidation of the biological effects of radon inhalation as a low-dose radiation.

Impact of low-dose X-ray radiation on the lipidome of Chlorella vulgaris

Impact of low-dose X-ray radiation on the lipidome of Chlorella vulgaris

Mitigating Oxidative Stress and Lung Fibrosis with Low Dose Radiation Therapy in Paraquat Poisoning: A Case Series

Paraquat poisoning, a frequent cause of fatalities in India, has become a significant public health issue, particularly among farmers. This herbicide, known for its high toxicity, results in severe pulmonary damage, with no specific antidote available. Ingestion of even small amounts of paraquat can lead to rapid multiorgan failure and death, largely due to its accumulation in the lungs, triggering oxidative stress and alveolar fibrosis. The toxicological mechanism involves the generation of free radicals that damage cellular membranes, eventually causing extensive lung fibrosis and alveolitis. Mortality rates remain high, with no definitive treatment. Recent advancements in low-dose radiotherapy (LDRT) have shown promise in treating lung injury caused by paraquat. LDRT’s anti-inflammatory properties have been previously explored in non-cancerous conditions like musculoskeletal disorders. Its ability to modulate inflammatory responses in lung tissue suggests potential benefits in mitigating paraquat-induced lung fibrosis. While preliminary evidence from small-scale studies has shown some improvement in patients treated with LDRT, the efficacy remains uncertain. At our center, we have treated five patients using LDRT, with mixed outcomes. Some patients showed improvement, while others succumbed to early pulmonary fibrosis. Further research is needed to establish the role of LDRT in managing paraquat poisoning. Larger studies are required to assess its ability to prevent lung fibrosis and improve long-term survival in patients with severe poisoning.

Association and small risk from low-dose radiation exposure

Association and small risk from low-dose radiation exposure

S6K1 Controls DNA Damage Signaling Modulated by the MRN Complex to Induce Radioresistance in Lung Cancer

Radiation is a mainstay of lung cancer treatment; however, resistance frequently develops. Identifying novel therapeutic targets to increase radiation sensitivity is crucial. S6K1 is a serine/threonine kinase known to regulate protein translation which is associated with radioresistance, but the mechanisms involved are unknown. We proposed to determine whether S6K1 promotes radioresistance by regulating DNA repair in lung cancer. Colony formation, protein expression and proliferation were assessed. S6K1 was modulated pharmacologically by either PF-4708671 or genetically by Crispr-Cas9. Higher radioresistance levels in lung cancer cells were associated with lower phosphoactivation of MRN complex members, a key activator of radiation-induced DNA repair signaling. We also found lower levels of p-ATM, a target of the MRN complex, in more radioresistant cells, which was associated with a lower expression of γ-H2AX cafter radiation. Further, genetic and pharmacological S6K1 targeting sensitized lung cancer cells to low doses of radiation (p ≤ 0.01). Additionally, S6K1−/− deletion increased the phosphoactivation of MRN complex members, indicating that S6K1 itself can shut down DNA damage regulated by MRN signaling. This is the first report showing that S6K1 inhibition radiosensitizes lung cancer cells by decreasing MRN complex-regulated DNA repair signaling. Future studies should evaluate the role of S6K1 as a target to overcome radioresistance.

The use of UV-A radiation for biofortification of lettuce and basil plants with antioxidant phenolic and flavonoid compounds

Stable plant production is a crucial concern of modern agriculture facing increasing food demands and the risk of less predictable weather conditions in the open field. Alternative approaches for plant production are greenhouses and indoor farming. Modern LED-based artificial lighting indoor facilities allow not only to fill the gap in the supply chain of food production, but to produce plants characterized with higher concentration of essential phytochemicals. Thus, in this study, we attempt to analyse the efficiency of short-term supplementation of spectrum within ultraviolet A light (UV-A, 365 nm) to increase the antioxidant potential of leafy plants, assessed by total phenolic (TPC) and flavonoid (TFC) content. To this end, two distinct cultivars of baby leaf lettuce (Lactuca sativa var. crispa L.) and microgreens basil (Ocimum basilicum L.) plants were grown under red-green-blue spectrum supplemented prior to harvest with low doses of UV-A radiation. Analyses showed that UV-A exposition enhanced TPC and TFC with green leaf cultivars, compared to dark-pigmented ones. The analysis also proved that plants exposed to UV-A presented higher overall antioxidant potential measured with 1,1-diphenyl-2-picrylhydrazil (DPPH). Results are crucial for better understanding the potential of UV-A supplementation to produce functional plants which are natural sources of dietary antioxidants.

Metal–organic frameworks as optically stimulated luminescence dosimeter

Metal–organic frameworks (MOF) have been vigorously investigated as hybrid materials in recent decades due to their exceptional structural versatility and applications in diverse fields. The development of novel MOFs for radiation detection and luminescence-based dosimetry is the latest topic of interest. In this contribution, we have synthesized and characterized a Uranyl MOF, which shows an optically stimulated luminescence (OSL) phenomenon induced by ionizing radiation. OSL dosimetric studies were carried out on Uranyl MOF, which revealed that MOF has a linear dose–response up to 100 Gy with a 1.1 Gy minimum detection dose. It also shows good reusability, around 30% fading in one day, very low fading beyond one day to 30 days, and decent radiation stability (stable up to 10 kGy). Preliminary dosimetry results are promising and show that Uranyl MOF can be utilized in the field of low-dose radiation processing applications in the future.