International journal of radiation biology最新文献

Purpose: The present study was carried out to evaluate the radioprotective activities of N-acetyl-L-tryptophan (L-NAT) using rodent and non-human primate (NHP) models.

Materials and methods: The antagonistic effect of L-NAT on the Transient receptor potential vanilloid-1 (TRPV1) receptor and substance P inhibition was determined using molecular docking and Elisa assays. The in vivo radioprotective activity of L-NAT was evaluated using whole-body survival assays in mice and NHPs. Radioprotective activity of L-NAT was also determined at the systemic level using quantitative histological analysis of bone marrow, jejunum, and seminiferous tubules of irradiated mice.

Results: Molecular docking studies revealed a strong binding of L-NAT with TRPV1 receptor at similar binding pockets to which capsaicin, an agonist of the TRPV1 receptor, binds. Further, capsaicin and gamma radiation were found to induce substance P levels in the intestines and serum of the mice, while L-NAT pretreatment was found to inhibit it. Significant whole-body survival (>80%) was observed in irradiated (9.0 Gy) mice that pretreated with L-NAT (150 mg/kg, b.wt. im) compared to 0% survival in irradiated mice that not pretreated with L-NAT. The quantitative histology of the hematopoietic, gastrointestinal, and male reproductive systems demonstrated significant protection against radiation-induced cellular degeneration. Interestingly, 100% survival was observed with irradiated NHPs (6.5 Gy) that pretreated with L-NAT (37.5 mg/kg, b.wt.im). Significant improvement in the hematology profile was observed after days 10-20 post-treatment periods in irradiated (6.5 Gy) NHPs that were pretreated with L-NAT.

Conclusion: L-NAT demonstrated excellent radioprotective activity in the mice and NHP models, probably by antagonizing TRPV1 receptor and subsequently inhibiting substance P expression.

Purpose: Cowpea (Vigna unguiculata (L.) Walp.) is a major legume crops for human consumption and livestock feed in tropical regions. Although its importance, the crop's production is subjected to numerous constraints, raising the need to develop outstanding genotypes. In this line, this study assesses the effects of gamma irradiation doses on cowpea genotypes to determine the LD50 and its effects on agro-morphological parameters.

Materials and methods: Healthy dry seeds of three cowpea genotypes, Bambey 21, Me51-M4-39M9, and Ndout violet pods (VP), were exposed to four doses of gamma-rays 0, 200, 300, and 400 Gy. Qualitative and quantitative parameters were evaluated since germination, and a two-way analysis of variance (ANOVA) was performed on the means of quantitative traits using R software.

Results: The results revealed that the LD50 on seed germination and plant survival ranged from 579 and 446.25 Gy, in Me51-M4-39M9, respectively. These values varied significantly among genotypes and revealed that low doses of gamma irradiation stimulated germination speed and had a positive effect on the early flowering of Ndout VP. Higher doses of gamma irradiation induced more severe mutations, causing visible effects such as changes in leaf color (albino, xantha, viridis, and variegation) and phyllotaxis. The frequency of chlorophyll mutants induced by gamma irradiation was found to be dose-genotype/dependent, with Bambey 21 being the most sensitive variety. Lower doses induced desirable mutations such as stem pigmentation and seed hilum coloration on Bambey 21 and Me51-M4-39M9. It has also had a positive impact on seedling height and leaf number in Bambey 21 and Ndout VP. However, high irradiation doses lead to a significant reduction in certain quantitative traits, such as plant height (PH), leaf length (LL), leaf width (LW), pod width (PWD), pod weight (PW), seed width (SWD), and seed weight. Analysis of the phenotypic performance of quantitative traits allowed us to cluster the four doses by genotype into three groups.

Conclusions: The optimum dose of gamma-irradiation in cowpea mutation breeding is genotype-dependent. The effects of gamma-irradiation on these traits and their relationships are highly dependent on the specific crop and genotype. Further research is needed to understand these effects underlying mechanisms and develop crop improvement strategies using gamma irradiation.

Background: Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms.

Methods: Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions.

Results: 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice.

Conclusions: Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

Purpose: Kernel texture plays a principal role in determining technological flour properties and end-use quality of wheat products. Hence, a multi-year mutation induction programme was conducted to isolate advanced wheat mutant lines with agro-morphologically superior performance, higher disease resistance and harder grain texture.

Materials and methods: Radiation mutagenesis was employed in soft textured wheat variety HPW 89 using gamma rays dose of 250, 300 and 350 Gy (Co⁶⁰: BARC, Mumbai) and evaluated across M_1-5 generations. Promising superior mutants selected were evaluated during M₄ and M₅ generation for induced variability and trait association for agro-morphological and quality traits. The screened mutants were also determined for induced changes at genetic level using gene specific markers for puroindoline genes.

Results: A total of 293 agro-morphologically superior mutants isolated showed significant genetic variation in the M₄ generation. Single kernel characterization system categorized 267 mutants (8.79-50.06) with higher grain hardness than the HPW 89 variety (7.39). Among these, 108 mutants were selected for agro-morphological and molecular characterization. Significant variations were found in these mutants in either pina and pinb or both puroindoline genes. Clustering among these mutants led to the formation of five clusters and a total of eleven mutants were found with better set of agro-morphological, disease resistance and quality traits.

Conclusion: These mutants can serve as important genetic resource for developing harder texture bread wheat varieties in the future grain quality improvement programmes. These mutants will also bridge the need of bakers and millers' requirement of varieties with specific texture and quality.

Purpose: Since the genotoxicity of ionizing radiation was demonstrated in the 1920s, its hereditary effects have remained a serious concern for human society. The International Commission on Radiological Protection has highlighted the need for appropriate protection against hereditary effects of radiation in humans. In this paper, we review the literature on the possible multigenerational and transgenerational effects following testicular exposure to radiation, focusing on sperm epigenetic alterations as possible mechanisms.

Results: This mini-review highlights that hereditary effects following testicular exposure occur via epigenetic changes of germ cells in animal models, providing implications on human radiation protection.

Conclusions: A great amount of epigenomic research data has emerged rapidly since the beginning of this century; thus, a revision of the radiological protection protocols against the hereditary effects of radiation would be no longer inevitable. The collection and analysis of evidence on these effects must be enhanced and further accelerated to formulate appropriate protection protocols in the future.

Purpose: This study focuses on analytical computer simulations performed to investigate a hypothetical event where the activation of a radiological dispersion device (RDD) triggers a crisis.

Materials and methods: The methodology presents steps centered on the initial evaluation phase of the event (initial 100 hours), aiming to evaluate the radiological risks regarding the development of leukemia. Local environmental changes, sex, and age were also used to assess risks.

Results: It was also estimated that the sex of potentially affected individuals was irrelevant to decisions at the early phase of the event. In contrast, age and the moment of release (day or night) were the most important variables influencing individual radiological risk.

Conclusions: Based on the calculated results, it was possible to conclude that the proposed methodology would significantly contribute to planning the allocation of human resources, reducing future risks.

Background: Human electromagnetic hypersensitivity (EHS) or electrosensitivity (ES) symptoms in response to anthropogenic electromagnetic fields (EMFs) at levels below current international safety standards are generally considered to be nocebo effects by conventional medical science. In the wider field of magnetoreception in biology, our understanding of mechanisms and processes of magnetic field (MF) interactions is more advanced.

Methods: We consulted a range of publication databases to identify the key advances in understanding of magnetoreception across the wide animal kingdom of life.

Results: We examined primary MF/EMF sensing and subsequent coupling to the nervous system and the brain. Magnetite particles in our brains and other tissues can transduce MFs/EMFs, including at microwave frequencies. The radical pair mechanism (RPM) is accepted as the main basis of the magnetic compass in birds and other species, acting via cryptochrome protein molecules in the eye. In some cases, extraordinary sensitivity is observed, several thousand times below that of the geomagnetic field. Bird compass disorientation by radio frequency (RF) EMFs is known.

Conclusions: Interdisciplinary research has established that all forms of life can respond to MFs. Research shows that human cryptochromes exhibit magnetosensitivity. Most existing provocation studies have failed to confirm EHS as an environmental illness. We attribute this to a fundamental lack of understanding of the mechanisms and processes involved, which have resulted in the design of inappropriate and inadequate tests. We conclude that future research into EHS needs a quantum mechanistic approach on the basis of existing biological knowledge of the magnetosensitivity of living organisms.

Repurposing therapeutic agents with existing clinical data is a common strategy for developing radiation countermeasures. IEPA (imidazolyl ethanamide pentandioic acid) is an orally bioavailable small molecule pseudopeptide with myeloprotective properties, a good clinical safety profile, and stable chemical characteristics facilitating stockpiling. Here, we evaluated IEPA's radiomitigative efficacy in the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) using total-body irradiation (TBI) models in C57BL/6J mice and WAG/RijCmcr rats, applying various posology schemes and introducing syringe feeding of the IEPA formulation in the pudding. Additionally, we assessed IEPA in the delayed effects of acute radiation exposure (DEARE) model after partial-body irradiation (PBI) in WAG/RijCmcr rats. Endpoints included survival, body weight, hematology, and pulmonary parameters, depending on the model. Results from mouse and rat TBI models demonstrated survival improvements with repeated IEPA dosing at 10 mg/kg, with the largest benefits observed in the bi-daily (BID) treatment over the 30-day ARS phase in female rats. Survival across PBI-DEARE subsyndromes was comparable between IEPA and vehicle groups, though IEPA improved pulmonary parameters in female rats during the lung-DEARE phase. Sex-related differences in response to irradiation and IEPA were noted, with females showing a survival advantage. IEPA treatment is compatible with Neulasta® (Pegfilgrastim; PEG-G-CSF); adequately powered studies are needed to confirm the trend toward improved survival over standard care alone. IEPA is a promising development candidate as a medical countermeasure against the effects of acute radiation syndrome. Further confirmatory studies in small and large animal models should validate the robustness and translatability of preliminary rodent data on IEPA's radiomitigative efficacy.

Background: Ionizing radiation can inflict cellular damage, the severity of which is determined by the dose, exposure duration, and its capacity to penetrate cells. Some studies have demonstrated that genetic and epigenetic mechanisms have enabled organisms to develop adaptive traits and enhance their ability to repair DNA damage. Northeastern Brazil, a region containing rocky outcrops rich in uranium and thorium, is an ideal scenario to study natural radiation and its effects on natural populations. This study presents evidence of radioresistance in the offspring of a natural strain of Drosophila melanogaster resident in the municipality of Cerro Corá (CC-res), an environment with high levels of radon-222.

Material and methods: Genotoxicity was assessed using the comet assay in offspring of the CC-res and Oregon-R (OR), the control group, both reared under the same laboratory conditions for between 7 and 13 months. The adults and their offspring larvae were exposed to the Cerro Corá environment for 6 days during the dry and wet seasons. Low damage index and frequency were observed only in the CC-res. To confirm the radioresistance, the same strains were exposed after 16 months of cultivation to controlled doses of gamma radiation.

Results and conclusions: CC-res exhibited significantly lower levels of damage compared to the OR strain, with a clear dose-response effect to the irradiation observed exclusively in the OR group. The results support the occurrence of radioresistance in the CC-res strain and underscore the need for further in vivo studies investigations into the impact of Brazil's natural environmental radiation.

Purpose: A substantial proportion of children with high risk Neuroblastoma die within the first 5 years post-diagnosis despite the complex treatment applied. In the recent years, tumor environment has been revealed as key factor for cancer treatment efficacy. In this sense, non-tumorigenic Neural Crest progenitor cells from high risk patients, have been described as part of Neuroblastoma stroma, promoting tumor growth and contributing to mesenchyme formation. In this paper we wanted to study the radiobiological behavior of these cells (NB14t) and how they influence the growth of tumorigenic neuroblasts after radiotherapy.

Materials and methods: To achieve our aim, we employed a wide list of methods either using NB14t cells as well as commercial NB cells. We have analyzed viability, survival, cell cyle profiles and differentiation. In addition, cocultured experiments were performed to monitor the influence of stroma cells to tumorigenic neuroblasts.

Results: We found that stromal progenitor cells showed an extraordinary radio-resistance either cultured in attached or suspension conditions. In good agreement, we found an enhanced repair of irradiation-induced DNA lesions as compared with commercial cell lines. In addition, according to our data these cells differentiate into a Cancer Associated Fibroblasts (CAFs)-like phenotype, hence contributing to the formation of mesenchymal stroma enhancing the growth of tumor cells after irradiation.

Conclusion: Our data show that neural progenitor cells from high risk NB stroma are radio-resistant and promote cancer growth after irradiation. This paper can help to understand the complex cell relationships within a tumor that will determine patient prognosis after radiotherapy.