Radiation research最新文献

{"title":"Induction of Chromosomal Aberrations after Exposure to the Auger Electron Emitter Iodine-125, the β--emitter Tritium and Cesium-137 γ rays.","authors":"M Unverricht-Yeboah, M Von Ameln, R Kriehuber","doi":"10.1667/RADE-23-00158.1","DOIUrl":"10.1667/RADE-23-00158.1","url":null,"abstract":"<p><p>High-LET-type cell survival curves have been observed in cells that were allowed to incorporate 125I-UdR into their DNA. Incorporation of tritiated thymidine into the DNA of cells has also been shown to result in an increase in relative biological effectiveness in cell survival experiments, but the increase is smaller than observed after incorporation of 125I-UdR. These findings are explained in the literature by the overall complexity of the induced DNA damage resulting from energies of the ejected electron(s) during the decay of 3H and 125I. Chromosomal aberrations (CA) are defined as morphological or structural changes of one or more chromosomes, and can be induced by ionizing radiation. Whether the number of CA is associated with the linear energy transfer (LET) of the radiation and/or the actual complexity of the induced DNA double-strand breaks (DSB) remains elusive. In this study, we investigated whether DNA lesions induced at different cell cycle stages and by different radiation types [Auger-electrons (125I), β- particles (3H), or γ radiation (137Cs)] have an impact on the number of CA induced after induction of the same number of DSB as determined by the γ-H2AX foci assay. Cells were synchronized and pulse-labeled in S phase with low activities of 125I-UdR or tritiated thymidine. For decay accumulation, cells were cryopreserved either after pulse-labeling in S phase or after progression to G2/M or G1 phase. Experiments with γ irradiation (137Cs) were performed with synchronized and cryopreserved cells in S, G2/M or G1 phase. After thawing, a CA assay was performed. All experiments were performed after a similar number of DSB were induced. CA induction after 125I-UdR was incorporated was 2.9-fold and 1.7-fold greater compared to exposure to γ radiation and radiation from incorporated tritiated thymidine, respectively, when measured in G2/M cells. In addition, measurement of CA in G2/M cells after incorporation of 125I-UdR was 2.5-fold greater when compared to cells in G1 phase. In contrast, no differences were observed between the three radiation qualities with respect to exposure after cryopreservation in S or G1 phase. The data indicate that the 3D organization of replicated DNA in G2/M cells seems to be more sensitive to induction of more complex DNA lesions compared to the DNA architecture in S or G1 cells. Whether this is due to the DNA organization itself or differences in DNA repair capability remains unclear.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Product Development within the National Institutes of Health Radiation and Nuclear Countermeasures Program.","authors":"David R Cassatt, Andrea L DiCarlo, Olivia Molinar-Inglis","doi":"10.1667/RADE-23-00144.1","DOIUrl":"10.1667/RADE-23-00144.1","url":null,"abstract":"<p><p>The Radiation and Nuclear Countermeasures Program (RNCP) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) was established to facilitate the development of medical countermeasures (MCMs) and diagnostic approaches for use in a radiation public health emergency. Approvals for MCMs can be very challenging but are made possible under the United States Food and Drug Administration (FDA) Animal Rule, which is designed to enable licensure of drugs or biologics when clinical efficacy studies are unethical or unfeasible. The NIAID portfolio includes grants, contracts, and inter-agency agreements designed to span all aspects of drug development and encompasses basic research through FDA approval. In addition, NIAID manages an active portfolio of biodosimetry approaches to assess injuries and absorbed radiation levels to guide triage and treatment decisions. NIAID, together with grantees, contractors, and other stakeholders with promising products, works to advance candidate MCMs and biodosimetry tools through an established product development pipeline. In addition to managing grants and contracts, NIAID tests promising candidates in our established preclinical animal models, and the NIAID Program Officers work closely with sponsors as product managers to guide them through the process. In addition, a valuable benefit for stakeholders is working with the NIAID Office of Regulatory Affairs, where NIAID coordinates with the FDA to facilitate interactions between sponsors and the agency. Activities funded by NIAID include basic research (e.g., library screens to discover new products, determine early efficacy, and delineate mechanism of action) and the development of small and large animal models of radiation-induced hematopoietic, gastrointestinal, lung, kidney, and skin injury, radiation combined injury, and radionuclide decorporation. NIAID also sponsors Good Laboratory Practice product safety, pharmacokinetic, pharmacodynamic, and toxicology studies, as well as efficacy and dose-ranging studies to optimize product regimens. For later-stage candidates, NIAID funds large-scale manufacturing and formulation development of products. The program also supports Phase 1 human clinical studies to ensure human safety and to bridge pharmacokinetic, pharmacodynamic, and efficacy data from animals to humans. To date, NIAID has supported >900 animal studies and one clinical study, evaluating >500 new/repurposed radiation MCMs and biodosimetric approaches. NIAID sponsorship led to the approval of three of the six drugs for acute radiation syndrome under the FDA Animal Rule, five Investigational New Drug applications, and 18 additional submissions for Investigational Device Exemptions, while advancing 38 projects to the Biomedical Advanced Research and Development Authority for follow-on research and development.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FSL-1: A Synthetic Peptide Increases Survival in a Murine Model of Hematopoietic Acute Radiation Syndrome.","authors":"Gregory P Holmes-Hampton, Vidya P Kumar, Kaylee Valenzia, Sanchita P Ghosh","doi":"10.1667/RADE-23-00142.1","DOIUrl":"10.1667/RADE-23-00142.1","url":null,"abstract":"<p><p>In the current geopolitical climate there is an unmet need to identify and develop prophylactic radiation countermeasures, particularly to ensure the well-being of warfighters and first responders that may be required to perform on radiation-contaminated fields for operational or rescue missions. Currently, no countermeasures have been approved by the U.S. FDA for prophylactic administration. Here we report on the efficacious nature of FSL-1 (toll-like receptor 2/6 agonist) and the protection from acute radiation syndrome (ARS) in a murine total-body irradiation (TBI) model. A single dose of FSL-1 was administered subcutaneously in mice. The safety of the compound was assessed in non-irradiated animals, the efficacy of the compound was assessed in animals exposed to TBI in the AFRRI Co-60 facility, the dose of FSL-1 was optimized, and common hematological parameters [complete blood cell (CBC), cytokines, and bone marrow progenitor cells] were assessed. Animals were monitored up to 60 days after exposure and radiation-induced damage was evaluated. FSL-1 was shown to be non-toxic when administered to non-irradiated mice at doses up to 3 mg/kg. The window of efficacy was determined to be 24 h prior to 24 h after TBI. FSL-1 administration resulted in significantly increased survival when administered either 24 h prior to or 24 h after exposure to supralethal doses of TBI. The optimal dose of FSL-1 administration was determined to be 1.5 mg/kg when administered prior to irradiation. Finally, FSL-1 protected the hematopoietic system (recovery of CBC and bone marrow CFU). Taken together, the effects of increased survival and accelerated recovery of hematological parameters suggests that FSL-1 should be developed as a novel radiation countermeasure for soldiers and civilians, which can be used either before or after irradiation in the aftermath of a radiological or nuclear event.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validating a Four-gene Set for H-ARS Severity Prediction in Peripheral Blood Samples of Irradiated Rhesus Macaques.","authors":"D Schwanke, S Schüle, S Stewart, O O Fatanmi, S Y Wise, C Hackenbroch, T Wiegel, V K Singh, M Port, M Abend, P Ostheim","doi":"10.1667/RADE-23-00162.1","DOIUrl":"10.1667/RADE-23-00162.1","url":null,"abstract":"<p><p>Increased radiological and nuclear threats require preparedness. Our earlier work identified a set of four genes (DDB2, FDXR, POU2AF1 and WNT3), which predicts severity of the hematological acute radiation syndrome (H-ARS) within the first three days postirradiation In this study of 41 Rhesus macaques (Macaca mulatta, 27 males, 14 females) irradiated with 5.8-7.2 Gy (LD29-50/60), including some treated with gamma-tocotrienol (GT3, a radiation countermeasure) we independently validated these genes as predictors in both sexes and examined them after three days. At the Armed Forces Radiobiology Research Institute/Uniformed Services University of the Health Sciences, peripheral whole blood (1 ml) of Rhesus macaques was collected into PAXgene® Blood RNA tubes pre-irradiation after 1, 2, 3, 35 and 60 days postirradiation, stored at -80°C for internal experimental analyses. Leftover tubes from these already ongoing studies were kindly provided to Bundeswehr Institute of Radiobiology. RNA was isolated (QIAsymphony), converted into cDNA, and for further gene expression (GE) studies quantitative RT-PCR was performed. Differential gene expression (DGE) was measured relative to the pre-irradiation Rhesus macaques samples. Within the first three days postirradiation, we found similar results to human data: 1. FDXR and DDB2 were up-regulated, FDXR up to 3.5-fold, and DDB2 up to 13.5-fold in the median; 2. POU2AF1 appeared down regulated around tenfold in nearly all Rhesus macaques; 3. Contrary to human data, DDB2 was more up-regulated than FDXR, and the difference of the fold change (FC) ranged between 2.4 and 10, while the median fold changes of WNT3, except days 1 and 35, were close to 1. Nevertheless, 46% of the Rhesus macaques showed down-regulated WNT3 on day one postirradiation, which decreased to 12.2% on day 3 postirradiation. Considering the extended phase, there was a trend towards decreased fold changes at day 35, with median-fold changes ranging from 0.7 for DDB2 to 0.1 for POU2AF1, and on day 60 postirradiation, DGE in surviving animals was close to pre-exposure values for all four genes. In conclusion, the diagnostic significance for radiation-induced H-ARS severity prediction of FDXR, DDB2, and POU2AF1 was confirmed in this Rhesus macaques model. However, DDB2 showed higher GE values than FDXR. As shown in previous studies, the diagnostic significance of WNT3 could not be reproduced in Rhesus macaques; this could be due to the choice of animal model and methodological challenges.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction for the ConRad 2023 Focus Issue.","authors":"Colonel Mc Prof Dr Matthias Port","doi":"10.1667/RADE-24-INTRO.1","DOIUrl":"https://doi.org/10.1667/RADE-24-INTRO.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PUM1 and PGK1 are Favorable Housekeeping Genes over Established Biodosimetry-related Housekeeping Genes such as HPRT1, ITFG1, DPM1, MRPS5, 18S rRNA and Others after Radiation Exposure.","authors":"R Muhtadi, S Stewart, F Bunert, O O Fatanmi, S Y Wise, C Gärtner, S Motzke, C Ruf, P Ostheim, S Schüle, D Schwanke, V K Singh, M Port, M Abend","doi":"10.1667/RADE-23-00160.1","DOIUrl":"10.1667/RADE-23-00160.1","url":null,"abstract":"<p><p>In gene expression (GE) studies, housekeeping genes (HKGs) are required for normalization purposes. In large-scale inter-laboratory comparison studies, significant differences in dose estimates are reported and divergent HKGs are employed by the teams. Among them, the 18S rRNA HKG is known for its robustness. However, the high abundance of 18S rRNA copy numbers requires dilution, which is time-consuming and a possible source of errors. This study was conducted to identify the most promising HKGs showing the least radiation-induced GE variance after radiation exposure. In the screening stage of this study, 35 HKGs were analyzed. This included selected HKGs (ITFG1, MRPS5, and DPM1) used in large-scale biodosimetry studies which were not covered on an additionally employed pre-designed 96-well platform comprising another 32 HKGs used for different exposures. Altogether 41 samples were examined, including 27 ex vivo X-ray irradiated blood samples (0, 0.5, 4 Gy), six X-irradiated samples (0, 0.5, 5 Gy) from two cell lines (U118, A549), as well as eight non-irradiated tissue samples to encompass multiple biological entities. In the independent validation stage, the most suitable candidate genes were examined from another 257 blood samples, taking advantage of already stored material originating from three studies. These comprise 100 blood samples from ex vivo X-ray irradiated (0-4 Gy) healthy donors, 68 blood samples from 5.8 Gy irradiated (cobalt-60) Rhesus macaques (RM) (LD29/60) collected 0-60 days postirradiation, and 89 blood samples from chemotherapy-(CTx) treated breast tumor patients. CTx and radiation-induced GE changes in previous studies appeared comparable. RNA was isolated, converted into cDNA, and GE was quantified employing TaqMan assays and quantitative RT-PCR. We calculated the standard deviation (SD) and the interquartile range (IQR) as measures of GE variance using raw cycle threshold (Ct) values and ranked the HKGs accordingly. Dose, time, age, and sex-dependent GE changes were examined employing the parametrical t-test and non-parametrical Kruskal Wallis test, as well as linear regression analysis. Generally, similar ranking results evolved using either SD or IQR GE measures of variance, indicating a tight distribution of GE values. PUM1 and PGK1 showed the lowest variance among the first ten most suitable genes in the screening phase. MRPL19 revealed low variance among the first ten most suitable genes in the screening phase only for blood and cells, but certain comparisons indicated a weak association of MRPL19 with dose (P = 0.02-0.09). In the validation phase, these results could be confirmed. Here, IQR Ct values from, e.g., X-irradiated blood samples were 0.6 raw Ct values for PUM1 and PGK1, which is considered to represent GE differences as expected due to methodological variance. Overall, when compared, the GE variance of both genes was either comparable or lower compared to 18S rRNA. Compared with the IQR GE values of","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation Biological Toximetry Using Circulating Cell-Free DNA (cfDNA) for Rapid Radiation/Nuclear Triage.","authors":"P. Okunieff, Steven G Swarts, Bruce Fenton, Stephen B Zhang, Zhenhuan Zhang, Lori Rice, Daohong Zhou, France Carrier, Lurong Zhang","doi":"10.1667/RADE-23-00159.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00159.1","url":null,"abstract":"Optimal triage biodosimetry would include risk stratification within minutes, and it would provide useful triage despite heterogeneous dosimetry, cytokine therapy, mixed radiation quality, race, and age. For regulatory approval, the U.S. Food and Drug Administration (FDA) Biodosimetry Guidance requires suitability for purpose and a validated species-independent mechanism. Circulating cell-free DNA (cfDNA) concentration assays may provide such triage information. To test this hypothesis, cfDNA concentrations were measured in unprocessed monkey plasma using a branched DNA (bDNA) technique with a laboratory developed test. Therefore, cfDNA concentration measurements are increasingly used in radiation oncology clinics to predict side effect risk. The cfDNA levels, along with hematopoietic parameters, were measured over a 7-day period in Rhesus macaques receiving total body radiation doses ranging from 1 to 6.5 Gy. Low-dose irradiation (0-2 Gy) was easily distinguished from high-dose whole-body exposures (5.5 and 6.5 Gy). Fold changes in cfDNA in the monkey model were comparable to those measured in a bone marrow transplant patient receiving a supralethal radiation dose, suggesting that the lethal threshold of cfDNA concentrations may be similar across species. Average cfDNA levels were 50 ± 40 ng/mL [±1 standard deviation (SD)] pre-irradiation, 120 ± 13 ng/mL at 1 Gy; 242 ± 71 ng/mL at 2 Gy; 607 ± 54 at 5.5 Gy; and 1585 ± 351 at 6.5 Gy (±1 SD). There was an exponential increase in cfDNA concentration with radiation dose. Comparison of the monkey model with the mouse model and the Guskova model, developed using Chernobyl responder data, further demonstrated correlation across species, supporting a similar mechanism of action. The test is available commercially in a Clinical Laboratory Improvement Amendments (CLIA) ready form in the U.S. and the European Union. The remaining challenges include developing methods for further simplification of specimen processing and assay evaluation, as well as more accurate calibration of the triage category with cfDNA concentration cutoffs.","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated Analysis of Radon Exposure and Lung Cancer Mortality in the Cohort of Newfoundland Fluorspar Miners (1950-2016).","authors":"Paul J. Villeneuve, Howard I. Morrison, R. Lane","doi":"10.1667/RADE-23-00114.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00114.1","url":null,"abstract":"The commercial mining of fluorspar in St. Lawrence Newfoundland began in 1933. Miners who worked underground were exposed to high levels of radon progeny, especially before ventilation was introduced into the mines in 1960. The mean cumulative radon exposure for underground miners in this cohort was 380.9 working level months (WLM). A series of studies of this cohort have characterized the increased risks of lung cancer mortality due to radon. We have extended the follow-up of this cohort an additional 15 years to provide additional insights on the risks of low levels of radon exposure, and the modifying effects of time since exposure, age at first exposure, attained age, duration of exposure, and cigarette smoking. The cohort consisted of 1,735 underground and 315 male surface miners who, combined, accrued 81,650 person-years of follow-up. The mortality experience of the cohort was determined from 1950-2016 through record linkage to Canadian national death data. Individual-level estimates of exposure to radon progeny, in WLMs, were determined for each year of employment. We compared the mortality experience of the underground miners to Newfoundland men using the standardized mortality ratio (SMR). Poisson regression models were fit to estimate excess relative risks (ERR) per 100 WLM. There were 236 lung cancer deaths identified, and of these, 221 occurred among underground workers. The SMR for lung cancer among underground miners compared to Newfoundland men was 2.67 (95% CI: 2.33, 3.04). The ERR per 100 WLM for lung cancer mortality, assuming a 5-year exposure lag, was 0.41 (95% CI: 0.23, 0.59). Attained age and time since exposure were important modifiers to the radon-lung cancer relationship. The joint relationship between smoking and radon on lung cancer risk was sub-additive, however, the smoking data were limited and available for only half of the cohort.","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140669753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Partial-Body, Continuous/Pulse Irradiation at Dose Rates from Flash to Conventional Rates on The Level of Surviving Blood Lymphocytes: Modeling Approach II. Two- and Multiple-Pulse Irradiation.","authors":"Francis A. Cucinotta, Olga A Smirnova","doi":"10.1667/RADE-23-00221.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00221.1","url":null,"abstract":"Mathematical models, which describe effects of partial-body, two- and multiple-pulse irradiation at high total doses D and at average dose rates N from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and mice, have been developed originating in the previously proposed approach. These models predict that levels of surviving blood lymphocytes in humans and mice increase with increasing the dose rate from N = D / TR (TR is the time of the blood flowing into or out of the irradiated segment of the blood circulatory system) to FLASH rates and approach an upper limiting level equal to (1- vR), where vR is the fraction of blood volume in the irradiated segment of the blood circulatory system. Levels of surviving blood lymphocytes computed at total doses D of 10-40 Gy and at average of dose rates N, which are equal to or exceed 40 Gy/s for humans and 400 Gy/s for mice, are nearly indistinguishable from the upper limiting level. These results can be interpreted as the models reproducing the optimal blood lymphocyte sparing in these mammals after such exposures. With decreasing the dose rate from N = D/ TR to conventional rates, at multiple-pulse irradiation the levels of surviving blood lymphocytes in humans and mice decrease to lower limiting levels, whereas at two-pulse irradiation they change cyclically and do not fall below their values for the delivery time equal to TR. Additionally, effects of two- and multiple-pulse irradiation of the whole abdomen in mice on the level of surviving blood lymphocytes are simulated within the developed models. Regimens of two- and multiple-pulse irradiation are taken the same as those reported in experiments, where effects of such exposures on the level of surviving crypts in mice were studied. Juxtaposing the modeling results with the experimental data reveals that the level of surviving blood lymphocytes in mice after two- and multiple-pulse irradiation of the abdomen at average dose rates N from FLASH to conventional rates modulates the level of surviving crypts in these animals after such exposures. A hypothesis is proposed to explain this phenomenon.","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140698848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Partial-Body, Continuous/Pulse Irradiation at Dose Rates from Flash to Conventional Rates on the Level of Surviving Blood Lymphocytes: Modeling Approach. I. Continuous Irradiation.","authors":"Francis A. Cucinotta, Olga A Smirnova","doi":"10.1667/RADE-23-00222.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00222.1","url":null,"abstract":"A mathematical model developed by Cucinotta and Smirnova is extended to describe effects of continuous, partial-body irradiation at high doses D and at dose N rates from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and small laboratory animals (mice). Specifically, whereas the applicability of the model is limited to the exposure times shorter than a single cardiac cycle T0, the extended model is capable of describing such effects for the aforementioned and longer exposure times. The extended model is implemented as the algebraic equations. It predicts that the level of surviving blood lymphocytes in humans and mice increases with increasing the dose rate from N = D / T0 to FLASH rates and approaches the upper limiting level of 1 - v R where v R is the fraction of blood volume in the irradiated part of the blood circulatory system. Levels of surviving blood lymphocytes computed at doses from 10 Gy to 40 Gy and at dose rates N, which equal or exceed 40 Gy/s for humans and 400 Gy/s for mice, are nearly indistinguishable from the upper limiting level. In turn, the level of surviving blood lymphocytes in humans and mice decreases with decreasing the dose rate from N = D / T0 to conventional rates and approaches a lower limiting level. This level strongly depends on the dose D (it is smaller at larger values of D) with a slight dependence on the dose rate N. The model with the parameters specified for mice (together with the model of the dynamics of lymphopoietic system in mice after partial-body irradiation) reproduce, on a quantitative level, the experimental data, according to which the concentration of blood lymphocytes measured in mice in one day after continuous, partial-body irradiation at a high dose and conventional dose rate is smaller at the larger value of vR. Additionally, the model predicts at the same high dose (>10 Gy) a faster restoration of the blood lymphocyte population in humans exposed to continuous, partial-body irradiation at a FLASH dose rate compared to a conventional dose rate.","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140701684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}