To investigate the dose-response relationship between radiation to the head and neck regions and damage observed in mice gustatory cells.

Radiation effect induced in nonirradiated cells which are adjacent or far from irradiated cells is termed radiation-induced bystander effect (RIBE). Published data on dose-response relationship of RIBE is controversial. In the present study the role of targeted and bystander cells in RIBE dose-response relationship of two cell lines have been investigated.

The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints.

The human population living in high level natural radiation areas (HLNRAs) of Kerala coast provide unique opportunities to study the biological effects of low dose and low dose rate ionizing radiation below 100 mGy. The level of radiation in this area varies from < 1.0 to 45 mGy/year. The areas with ≤ 1.50 mGy/year are considered as normal level natural radiation areas (NLNRA) and > 1.50 mGy/year, as high level natural radiation areas (HLNRA). The present study evaluated dose response relationship between DNA double strand breaks (DSBs) and background radiation dose in individuals residing in Kerala coast. Venous blood samples were collected from 200 individuals belonging to NLNRA (n = 50) and four dose groups of HLNRA; 1.51-5.0 mGy/year (n = 50), 5.01-10.0 mGy/year (n = 30), 10.01-15.0 mGy/year (n = 33), > 15.0 mGy/year (n = 37) with written informed consent. The mean dose of NLNRA and four HLNRA dose groups studied are 1.21 ± 0.21 (range: 0.57-1.49), 3.02 ± 0.95 (range: 1.57-4.93), 7.43 ± 1.48 (range: 5.01-9.75), 12.22 ± 1.47 (range: 10.21-14.99), 21.64 ± 6.28 (range: 15.26-39.88) mGy/year, respectively. DNA DSBs were quantified using γH2AX as a marker, where foci were counted per cell using fluorescence microscopy.

First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver's disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99mTc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90Y-PET/CT and assess the dose-response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43-82). Patients underwent MRI/CT, 18F-FDG-PET/CT before and 3-6 months post-SIRT, and 90Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99mTc-MAA-SPECT/CT and post-SIRT 90Y-PET/CT, and assessed with Lin's concordance correlation coefficients (ρc and Cb), Pearson's coefficient correlation (ρ), and Bland-Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46-1586 Gy). Concordance between 99mTc-MAA-SPECT/CT and 90Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) (ρ = 0.725, ρc = 0.703, Cb = 0.969) with good agreement (mean difference: - 4.93 ± 218.3 Gy, 95%LOA: - 432.8-422.9). Without RC correction, concordance was better for resin microspheres (ρ = 0.85, ρc = 0.998, Cb = 0.849) and agreement was very good between predictive 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (mean difference: - 4.05 ± 55.9 Gy; 95%LOA: - 113.7-105.6). After RC correction, 99mTc-MAA-SPECT/CT dosimetry overestimated AD (- 70.9 ± 158.9 Gy; 95%LOA: - 382.3-240.6). For glass microspheres, concordance markedly improved with RC correction (ρ = 0.790, ρc = 0.713, Cb = 0.903 vs without correction: ρ = 0.395, ρc = 0.244, Cb = 0.617) and 99mTc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: - 375.4-673.2). For non-tumor liver, concordance was good between 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (ρ = 0.942, ρc = 0.852, Cb = 0.904). 99mTc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose-response threshold could be identified. 99mTc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.

The relationship between solar ultraviolet radiation and the risk of breast cancer is conflicting. The purpose of our study was to quantitatively assess the relationship between solar ultraviolet radiation and breast cancer risk and to analyze related factors such as age and sunscreen use.Articles indexed in PubMed and Embase and published between January 2005 and March 2020 were searched for relevant keywords. The relative risk was calculated using random-effect or fixed-effect models in the meta-analysis and dose-response meta-analysis, which were conducted according to the Meta-Analyses of Observational Studies in Epidemiology reporting guidelines. Sensitivity analyses for heterogeneity and publication bias were evaluated.Six studies were eligible for inclusion in the meta-analysis, and three of these were included in the dose-response analysis. We found a correlation between exposure to solar ultraviolet radiation and breast cancer risk (relative risk: 0.70, 95% confidence interval: 0.65, 0.75). We also found a linear dose-response relationship between the exposure and breast cancer risk (relative risk: 0.86, 95% confidence interval: 0.81, 0.91) in women over 40. Not tanning and covering the limbs were associated with breast cancer risk, but sunscreen use was not.Exposure to solar ultraviolet radiation is negatively correlated with breast cancer risk, and the association is linear in women over 40. This is the first dose-response meta-analysis on the topic, and the influence of factors such as estrogen receptor status, occupational exposure, and ethnicity requires in-depth study.

Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08-1.14] and OR = 1.09 [CI 1.06-1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120-180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17-5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose-response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments.

Characterization of biological and chemical responses to ionizing radiation by various organisms is essential for potential applications in bioremediation, alternative modes of detecting nuclear material, and national security. Escherichia coli DH10β is an optimal system to study the microbial response to low-dose ionizing radiation at the transcriptional level because it is a well-characterized model bacterium and its responses to other environmental stressors, including those to higher radiation doses, have been elucidated in prior studies. In this study, RNA sequencing with downstream transcriptomic analysis (RNA-seq) was employed to characterize the global transcriptional response of stationary-phase E. coli subjected to 239Pu, 3H (tritium), and 55Fe, at an approximate absorbed dose rate of 10 mGy day-1 for 1 day and 15 days. Differential expression analysis identified significant changes in gene expression of E. coli for both short- and long-term exposures. Radionuclide source exposure induced differential expression in E. coli of genes involved in biosynthesis pathways of nuclear envelope components, amino acids, and siderophores, transport systems such as ABC transporters and type II secretion proteins, and initiation of stress response and regulatory systems of temperature stress, the RpoS regulon, and oxidative stress. These findings provide a basic understanding of the relationship between low-dose exposure and biological effect of a model bacterium that is critical for applications in alternative nuclear material detection and bioremediation. IMPORTANCE Escherichia coli strain DH10β, a well-characterized model bacterium, was subjected to short-term (1-day) and long-term (15-day) exposures to three different in situ radiation sources comprised of radionuclides relevant to nuclear activities to induce a measurable and identifiable genetic response. We found E. coli had both common and unique responses to the three exposures studied, suggesting both dose rate- and radionuclide-specific effects. This study is the first to provide insights into the transcriptional response of a microorganism in short- and long-term exposure to continuous low-dose ionizing radiation with multiple in situ radionuclide sources and the first to examine microbial transcriptional response in stationary phase. Moreover, this work provides a basis for the development of biosensors and informing more robust dose-response relationships to support ecological risk assessment.

The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC).

One of the characteristics of Prostate-Specific Antigen (PSA) is PSA slope. It is the rate of diminishing PSA marker over time after radiotherapy (RT) in prostate cancer (PC) patients. The purpose of this study was to evaluate the relationship between increasing RT doses and PSA slope as a potential surrogate for PC recurrence.

Background Subclinical left ventricular dysfunction detected by 2-dimensional global longitudinal strain post breast radiotherapy has been described in patients with breast cancer. We hypothesized that left ventricular dysfunction postradiotherapy may be site specific, based on differential segmental radiotherapy dose received. Methods and Results Transthoracic echocardiograms were performed at baseline, 6 weeks, and 12 months postradiotherapy on 61 chemotherapy-naïve women with left-sided breast cancer undergoing tangential breast radiotherapy. Radiation received within basal, mid, and apical regions for the 6 left ventricular walls was quantified from the radiotherapy treatment planning system. Anterior, anteroseptal, and anterolateral walls received the highest radiation doses, while inferolateral and inferior walls received the lowest. There was a progressive increase in the radiation dose received from basal to apical regions. At 6 weeks, the most significant percentage deterioration in strain was seen in the apical region, with greatest reductions in the anterior wall followed by the anteroseptal and anterolateral walls, with a similar pattern persisting at 12 months. There was a within-patient dose-response association between the segment-specific percentage deterioration in strain at 6 weeks and 12 months and the radiation dose received. Conclusions Radiotherapy for left-sided breast cancer causes differential segmental dysfunction, with myocardial segments that receive the highest radiation dose demonstrating greatest strain impairment. Percentage deterioration in strain observed 6 weeks postradiotherapy persisted at 12 months and demonstrated a dose-response relationship with radiotherapy dose received. Radiotherapy-induced subclinical cardiac dysfunction is of importance because it could be additive to chemotherapy-related cardiotoxicity in patients with breast cancer. Long-term outcomes in patients with asymptomatic strain reduction require further investigation.

Regional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer.

Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.

Ionizing radiation from natural sources or anthropogenic activity has the potential to cause oxidative stress or genetic damage in living organisms, through the ionization and excitation of molecules and the subsequent production of free radicals and reactive oxygen species (ROS). The present work focuses on radiation-induced biological effects using the zebrafish (Danio rerio) vertebrate model. Changes in developmental traits and gene expression in zebrafish were assessed after continuous external gamma irradiation (0.4, 3.9, 15 and 38 mGy/h) with corresponding controls, starting at 2.5 hours post fertilization (hpf) and lasting through embryogenesis and the early larval stage. The lowest dose rate corresponded to recommended benchmarks at which adverse effects are not expected to occur in aquatic ecosystems (2-10 mGy/day). The survival observed at 96 hours post fertilization (hpf) in the 38 mGy/h group was significantly lower, while other groups showed no significant difference compared to controls. The total hatching was significantly lower from controls in the 15 mGy/h group and a delay in hatching onset in the 0.4 mGy/h group was observed. The deformity frequency was significantly increased by prolonged exposure duration at dose rates ≥ 0.4 mGy/h. Molecular responses analyzed by RNA-seq at gastrulation (5.5 hpf transcriptome) indicate that the radiation induced adverse effects occurred during the earliest stages of development. A dose-response relationship was found in the numbers of differentially regulated genes in exposure groups compared to controls at a total dose as low as 1.62 mGy. Ingenuity Pathway Analysis identified retinoic acid receptor activation, apoptosis, and glutathione mediated detoxification signaling as the most affected pathways in the lower dose rate (0.54 mGy/h), while eif2 and mTOR, i.e., involved in the modulation of angiogenesis, were most affected in higher dose rates (5.4 and 10.9 mGy/h). By comparing gene expression data, myc was found to be the most significant upstream regulator, followed by tp53, TNF, hnf4a, TGFb1 and cebpa, while crabp2b and vegfab were identified as most frequent downstream target genes. These genes are associated with various developmental processes. The present findings show that continuous gamma irradiation (≥ 0.54 mGy/h) during early gastrula causes gene expression changes that are linked to developmental defects in zebrafish embryos.

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

The study of cell survival following exposure to nonuniform radiation fields is taking on particular interest because of the increasing evidence of a nonlinear relationship at low doses. We conducted in vitro experiments using the MCF7 breast cancer cell line. A 2.4 × 2.4 cm(2) square area of a T25 flask was irradiated by a Varian Novalis accelerator delivering 6 MV photons. Cell survival inside the irradiation field, in the dose gradient zone and in the peripheral zone, was determined using a clonogenic assay for different radiation doses at the isocenter. Increased cell survival was observed inside the irradiation area for doses of 2, 10, and 20 Gy when nonirradiated cells were present at the periphery, while the cells at the periphery showed decreased survival compared to controls. Increased survival was also observed at the edge of the dose gradient zone for cells receiving 0.02 to 0.01 Gy when compared with cells at the periphery of the same flask, whatever the isocenter dose. These data are the first to report cell survival in the dose gradient zone. Radiotherapists must be aware of this nonlinearity in dose response.

Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Radiation-induced lung fibrosis (RILF) is considered a critical determinant for late normal tissue complications. While RILF mouse models are frequently approached e.g., as a single high dose thoracic irradiation to investigate lung fibrosis and candidate modulators, a systematic radiobiological characterization of RILF mouse model is urgently needed to compare relative biological effectiveness (RBE) of particle irradiation with protons, helium-, carbon and oxygen ions now available at HIT. We aimed to study the dose-response relationship and fractionation effect of photon irradiation in development of pulmonary fibrosis in C57BL/6 mouse.

Enhanced cellular DNA repair efficiency and suppression of genomic instability have been proposed as mechanisms underlying radio-adaptive responses following low-dose radiation exposures. We previously showed that low-dose γ irradiation does not generate radio-adaptation by lowering radiation-induced cytogenetic damage in mouse spleen. Since radiation may exert tissue-specific effects, we extended these results here by examining the effects of γ radiation on cytogenetic damage and proliferative index in bone marrow erythrocytes of C57BL/6 and BALB/c mice. In C57BL/6 mice, the induction of micronuclei in polychromatic erythrocytes (MN-PCE) was observed at radiation doses of 100 mGy and greater, and suppression of erythroblast maturation occurred at doses of >500 mGy. A linear dose-response relationship for MN-PCE frequencies in C57BL/6 mice was established for radiation doses between 100 mGy and 1 Gy, with departure from linearity at doses of >1 Gy. BALB/c mice exhibited increased MN-PCE frequencies above baseline following a 20 mGy radiation exposure but did not exhibit radio-sensitivity relative to C57BL/6 mice following 2 Gy exposure. Radio-adaptation of bone marrow erythrocytes was not observed in either strain of mice exposed to low-dose priming γ irradiation (single doses of 20 mGy or 100 mGy or multiple 20 mGy doses) administered at various times prior to acute 2 Gy irradiation, confirming the lack of radio-adaptive response for induction of cytogenetic damage or suppression or erythrocyte proliferation/maturation in bone marrow of these mouse strains.

The cytokinesis-block micronucleus assay in peripheral blood lymphocytes is an established technique for biodosimetry. The aim of this project was to generate a X-ray induced micronuclei (MN) curve for peripheral blood lymphocytes taken from five healthy donors. The blood samples were irradiated with X-rays of 122 KeV at a dose rate of 0.652 Gy/min to doses of 0.5, 1, 2, 3, and 4 Gy. The blood samples were then cultured for 72 h at 37°C and processed following the International Atomic Energy Agency standard procedure with slight modifications. The result showed that the yields of MN frequencies were increased with the increase of radiation dose. Reconstruction of the relationship of MN with dose was fitted to a linear-quadratic model using Chromosome Aberration Calculation Software version 2.0. Due to their advantages, mainly, the dependence on radiation dose and dose rate, despite their limitation, these curves will be useful as alternative method for in vitro dose reconstruction and can support the preparedness for public or occupational radiation overexposure and protection. The results reported here also give us confidence to apply the obtained calibration curve of MN for future biological dosimetry requirements in Indonesia.

Purpose: This study investigated the association between radiation dose and complication rate in patients who underwent breast reconstruction to understand the role of radiation hypofractionated regimen, boost radiation therapy (RT), and RT techniques. Methods: We retrospectively evaluated 75 patients treated with post-mastectomy adjuvant RT for breast cancer in the setting of two-stage prosthetic breast reconstruction. Near maximum radiation dose (Dmax) in the 2 or 0.03 cc of reconstructed breast or overlying breast skin was obtained from dose-volume histograms. Results: Post-RT complications occurred in 22.7% of patients. Receiver operating characteristic analysis showed that all near Dmax parameters were able to predict complication risk, which retained statistical significance after adjusting other variables (odds ratio 1.12 per Gy, 95% confidence interval 1.02-1.23) with positive dose-response relationship. In multiple linear regression model (R 2 = 0.92), conventional fractionation (β = 11.7) and 16 fractions in 2.66 Gy regimen (β = 3.9) were the major determinants of near Dmax compared with 15 fractions in 2.66 Gy regimen, followed by utilization of boost RT (β = 3.2). The effect of bolus and dose inhomogeneity seemed minor (P > 0.05). The location of hot spot was not close to the high density metal area of the expander, but close to the surrounding areas of partially deflated expander bag. Conclusions: This study is the first to demonstrate a dose-response relationship between risk of complications and near Dmax, where hypofractionated regimen or boost RT can play an important role. Rigorous RT-quality assurance program and modification of dose constraints could be considered as a critically important component for ongoing trials of hypofractionation. Based on our findings, we initiated a multi-center retrospective study (KROG 18-04) and a prospective study (NCT03523078) to validate our findings.