Radiation Research

Radioresistance restrains the therapeutic effect of nasopharyngeal carcinoma (NPC). Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 sensitized NPC cells to radiation and to explore the possible mechanisms. Our results revealed that Rg3 increased radiosensitivity in both HNE1 and CNE2 cell lines. Radiation-induced epithelial mesenchymal transition (EMT) in NPC cells and Rg3 blocked this effect...

Radiation models, such as whole thorax lung irradiation (WTLI) or partial-body irradiation (PBI) with bone-marrow sparing, have shown that affected lung tissue displays a continual progression of injury, often for months after the initial insult. Undoubtably, a variety of resident and infiltrating cell types either contribute to or fail to resolve this type of progressive injury, which in lung tissue, often develops into lethal and irreversible radiation-induced pulmonary fibrosis (RIPF), indicating a failure of the lung to return to a homeostatic state...

Human papillomavirus (HPV) infection is strongly associated with cervical cancer (CC). Genomic alterations caused by viral infection and subsequent dysregulation of cellular metabolism under hypoxic conditions could influence the response to treatment. We studied a possible influence of IGF-1Rβ, hTERT, HIF1α, GLUT1 protein expression, HPV species presence and relevant clinical parameters on the response to treatment. In 21 patients, HPV infection and protein expression were detected using GP5+/GP6+PCR-RLB and immunohistochemistry, respectively...

Alzheimer's Disease (AD) represents a major health problem without effective treatments. As the incidence of the disease will continue to rise, it is imperative to find new treatment options to halt or slow disease progression. In recent years, several groups have begun to study the utility of low total dose radiation therapy (LTDRT) to inhibit some of the pathological features of AD and improve cognition in a variety of animal models. These preclinical studies have led to Phase 1 and 2 trials in different centers around the world...

The present paper reviews the uncertainties and errors in complex dosimetry systems that were developed to estimate individual doses in different post-Chernobyl (Chornobyl) radiation epidemiology studies among the general population and the cleanup workers. These uncertainties and errors are associated with (i) instrumental radiation measurements of humans and environmental samples, (ii) inherent uncertainties arising from the stochastic random variability of the parameters used in exposure assessment and from a lack of knowledge about the true values of the parameters, and (iii) human factor uncertainties due to poor memory recall resulting in incomplete, inaccurate, or missing responses during personal interview with study subjects conducted long after exposure...

The objective of the current study was to establish a mouse model of acute radiation syndrome (ARS) after total-body irradiation with 2.5% bone marrow sparing (TBI/BM2.5) that progressed to the delayed effects of acute radiation exposure, specifically pneumonitis and/or pulmonary fibrosis (DEARE-lung), in animals surviving longer than 60 days. Two hundred age and sex matched C57L/J mice were assigned to one of six arms to receive a dose of 9.5 to 13.25 Gy of 320 kV X-ray TBI/BM2.5. A sham-irradiated cohort was included as an age- and sex-matched control...

Altered cellular responses to DNA damage can contribute to cancer development, progression, and therapeutic resistance. Mutations in key DNA damage response factors occur across many cancer types, and the DNA damage-responsive gene, TP53, is frequently mutated in a high percentage of cancers. We recently reported that an alternative splicing pathway induced by DNA damage regulates alternative splicing of TP53 RNA and further modulates cellular stress responses. Through damage-induced inhibition of the SMG1 kinase, TP53 pre-mRNA is alternatively spliced to generate TP53β mRNA and p53β protein is required for optimal induction of cellular senescence after ionizing radiation-induced DNA damage...

Biological dosimetry is a key technique for retrospective radiation dosimetry that provides individual estimates of absorbed dose of ionizing radiation, applicable for use in a large scale radiological/nuclear event. Current techniques for biodosimetry are labor intensive and time consuming and not high through-put. In this proof-of-concept study, we developed a new approach for detecting irradiated blood based on Raman spectroscopy of blood combined with multivariate analysis. Peripheral blood samples from 8 healthy male and female, anonymous donors, were exposed to either 5 Gy X ray radiation or unirradiated (0 Gy)...

The cytokinesis-block micronucleus (CBMN) assay in cytogenetic biodosimetry uses micronucleus (MN) frequency scored in binucleated cells (BNCs) to estimate ionizing radiation dose exposed. Despite the faster and simpler MN scoring, CBMN assay is not commonly recommended in radiation mass-casualty triage as human peripheral blood is typically cultured for 72 h. Furthermore, CBMN assay evaluation in triage often uses high-throughput scoring with expensive and specialized equipment. In this study, we evaluated the feasibility of a low-cost method of manual MN scoring on Giemsa-stained slides in shortened 48 h cultures for triage...

Tritium is found in the environment under three forms: free in the water, gaseous, and bound to organic matter. Once internalized in living organisms, it can be found in two forms: tissue free water tritium (TFWT) and organically bound tritium (OBT). This study aims to better understand OBT internalization in living organisms and to show the complementarity between experimental procedures and microdosimetry simulations that have often been used to obtain more information on imparted energy to cell nuclei. To do so, tritiated thymidine, an organic form of tritium, was chosen and zebrafish embryos [3...

To explore the likely prevalence of false indications of dose-response nonlinearity in large epidemiologic cancer radiation cohort studies (A-bomb survivors, INWORKS, Techa River). Reasons: Increasing numbers of tests of nonlinearity are being made in studies. Hypothesized nonlinear dose-response models have been justified to policy makers by analyses that rely in part on isolated findings that could be statistical fluctuations. After removing dose nonlinearity (linearization) by adjusting person-years of observation at each dose category, indications of nonlinearity, necessarily false, were counted in 5,000 randomized replications of six datasets...

Radiation-induced heart injury (RIHI) limits the dose delivery of radiotherapy for thoracic cancer. Shenmai injection (SMI) is reported to have potential cytoprotective properties and is commonly used in cardiovascular diseases. So, we aimed to investigate the potential protective effects of SMI treatment on RIHI. In this study, we established the RIHI model using Sprague-Dawley rats and H9c2 cell line. In vivo, the biochemical assay was used to measure serum cardiac injury- related biomarkers and echocardiography to evaluate heart function...

Cardiotoxicity is a well-recognized, serious adverse effect of thoracic radiation therapy. This study aimed to evaluate longitudinal electrocardiogram (ECG) changes in patients receiving thoracic radiation therapy and identify correlating factors that can predict the risk of cardiotoxicity. This retrospective study included 202 patients treated with thoracic radiation therapy, and chemotherapy and targeted therapy were allowed. Mean heart dose (MHD) was evaluated on dose-volume histograms. ECG, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal B-type natriuretic peptide (NT-proBNP) analyses were conducted before irradiation and during the follow-up period of 6-12 months (average 8 months)...

SAG (sensitive to apoptosis gene)/RBX2 (RING box-2), is the second family member of RING component of cullin-RING ligase (CRL) complex required for its enzymatic activity. Using total or conditional Sag knockout mouse models, we previously showed that Sag plays an essential role in embryonic development, apoptosis, vasculogenesis, angiogenesis and tumorigenesis. We also found that Sag-null ES cells are more sensitive to radiation. In this study, we generated the SagΔ/fl-neo mice with partial Sag inactivation due to deletion in one allele (Δ allele), and disrupted expression in the another (by a neo cassette)...

Among the various types of cell death induced by ionizing radiation, apoptosis is a highly regulated and well-characterized form. Investigating radiation-induced apoptosis in an intact organism offers advantages in capturing the dynamics of apoptosis under preserved physiology, although high resolution imaging remains challenging. Owing to their optical transparency and genetic amenability, zebrafish is an ideal animal model for research into this aspect. In this study, we present a secA5 transgenic zebrafish expressing genetically encoded secreted ANNEXIN V fused with mVenus, a yellow fluorescent protein that enables reporting of radiation-induced apoptosis...

In 2017, a special edition of Radiation Research was published [Oct; Vol. 188 4.2 (https://bioone.org/journals/radiation-research/volume-188/issue-4.2)] which focused on a recently established radiobiology project within SNOLAB, a unique deep-underground research facility. This special edition included original articles, reviews and commentaries relevant to the research goals of this new project which was titled Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR). These research goals were founded in understanding the biological effects of terrestrial and cosmic natural background radiation (NBR)...

Recently, long noncoding RNAs (lncRNAs) and the Warburg effect have been reported to play important roles in the radio-sensitivity of tumor cells. Survival correlates with pathologic responses to chemoradiotherapy and improving responses to radiation may translate into improved survival. This study aims to examine the effects and mechanisms of lncRNA DGCR5 and the Warburg effect on ESCC cell radio-sensitivity. Levels of DGCR5, miR-195 and hexokinase 2 (HK2) expression in ESCC tissues and cells were determined and their clinical significance was analyzed...

Radiation-induced intestinal injury is one the most common adverse events of radiotherapy, which can severely affect quality of life. There are currently no effective preventive and therapeutic options for this disorder. Quercetin is a natural flavonoid found in common food species, with the characteristics of antioxidative, anti-inflammatory, and anti-cancerous activity. However, the role of quercetin on radiation-induced intestinal injury and the underlying mechanism remains poorly understood. In this study, we found quercetin treatment can improve the survival rate of mice after a single-dose (10 Gy) abdominal irradiation...

A mathematical model, which describes the level of surviving lymphocytes in the blood after ultra-high (FLASH) and lower dose rates of partial-body irradiation, is developed. The model is represented by simple analytic formulae that involve a few parameters, namely, physiologic parameters (characteristics of the blood flow through the blood circulatory system and its irradiated part), a biophysical parameter (a characteristic of the blood lymphocytes radiosensitivity), and the physical parameters (characteristics of irradiation)...

Acute exposure to high dose radiation can cause acute radiation syndrome (ARS), a potentially life-threatening illness. Individuals that survive ARS are at risk of developing the delayed effects of acute radiation exposure, with the lungs being particularly susceptible (DEARE-lung). For individuals at risk of radiation exposure, there are no Food and Drug Administration-approved medical countermeasures (MCMs) for prophylactic or post-exposure use that can prevent or mitigate DEARE-lung. BIO 300 is a novel formulation of synthetic genistein that has been extensively studied as a prophylactic MCM for the hematopoietic subsyndrome of ARS (H-ARS)...