International Journal of Radiation Biology最新文献

Purpose: Transcriptomic-based approaches are being developed to meet the needs for large-scale radiation dose and injury assessment and provide population triage following a radiological or nuclear event. This review provides background and definition of the need for new biodosimetry approaches, and summarizes the major advances in this field. It discusses some of the major model systems used in gene signature development, and highlights some of the remaining challenges, including individual variation in gene expression, potential confounding factors, and accounting for the complexity of realistic exposure scenarios.

Conclusions: Transcriptomic approaches show great promise for both dose reconstruction and for prediction of individual radiological injury. However, further work will be needed to ensure that gene expression signatures will be robust and appropriate for their intended use in radiological or nuclear emergencies.

Purpose: This manuscript is a scholarly perspective on the crucially important topic of mentoring in STEM and the STEM-intensive health professions (STEM+). Our purpose is to share our understanding of this subject as a means to mitigate the persistent underrepresentation in these fields and to offer our recommendations.

Materials & methods: This manuscript draws on the literature and our experiences to develop recommendations for improving outcomes for diverse populations of undergraduate students who are pursuing majors in the STEM fields and aspire to careers in the biomedical sciences and/or STEM-intensive health professions.

Results: Undergraduate learning communities and mentored research activities promote continued engagement in STEM and also provide a competitive foundation for careers in these fields.

Conclusions: (1) Mentoring must be brought to scale through clearly articulated institutional and disciplinary prioritization of learning communities, with attendant assessment to monitor the impact of creating an environment that supports diverse students from underrepresented backgrounds. (2) Individual faculty members and principal investigators affiliated with academic institutions and stand-alone research facilities can enhance their mentoring role by welcoming underrepresented undergraduates into their laboratories. (3) Faculty members, administrators, and staff members must commit themselves to the success of each student who enrolls in a STEM + program, rather than accepting high rates of failure as inevitable. (4) Increased interactions between first-year students and faculty members through experiences in mentored learning communities that promote authentic engagement and discovery are key to promoting the retention of diverse populations of students who are underrepresented in the STEM + fields. (5) Learning communities can amplify the impact of an individual mentor. (6) Barriers to student success, such as weak preparation from high school courses, must be proactively and effectively addressed.

Purpose: Assessing alterations in the expression of radiation-responsive genes in peripheral blood cells is considered a promising approach for high-throughput radiation biodosimetry. However, optimization of conditions for storage and transport of blood samples would be critical for obtaining reliable results. Recent studies involved the incubation of isolated peripheral blood mononuclear cells (in cell culture medium) and/or use of RNA stabilizing agents for sample storage, immediately after the ex vivo irradiation of whole blood. We used a simpler protocol by incubating undiluted peripheral whole blood without any RNA stabilizing agent, and studied the impact of storage temperature and incubation time on the expression levels of 19 known radiation responsive genes.

Materials & methods: Peripheral whole blood was γ-irradiated ex vivo at room temperature at low (0.5 Gy), moderate (1 Gy, 2 Gy) and high (4 Gy) doses and immediately incubated at two different temperatures at 4 °C or 37 °C for 2h, 4h and 24 h. Using qRT-PCR, mRNA expression levels of CDKN1A, DDB2, GADD45A, FDXR, BAX, BBC3, MYC, PCNA, XPC, ZMAT3, AEN, TRIAP1, CCNG1, RPS27L, CD70, EI24, C12orf5, TNFRSF10B, ASCC3 were analyzed at respective time-points and compared with the sham-irradiated controls.

Results: Transcriptional responses of all 19 genes did not alter significantly upon incubation of whole blood samples at 4 °C, as compared to untreated controls. However, incubation at 37 °C for 24 h resulted in significant radiation-induced overexpression in 14 out of the 19 genes analyzed (except CDKN1A, BBC3, MYC, CD 70 and EI24). Detailed patterns during incubation at 37 °C revealed time-dependent up-regulation of these genes, with DDB2 and FDXR showing significant up-regulation both at 4 and 24 h with the highest fold-change observed.

Conclusion: Overall, the undiluted whole blood incubated at 37 °C for 24 h was found to elicit most optimal transcriptional response in the genes studied, with most profound overexpression of DDB2 and FDXR. We propose that sample storage/transport/post-transit incubation at the physiological temperature for up to 24 h may enhance the sensitivity of gene expression based biodosimetry and facilitate its usage for triage application.

Purpose: The aim of this study was to evaluate if the micronucleus test using oral epithelial cells is a suitable biomarker for biomonitoring children exposed to X-ray.

Material and methods: A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to February 2022 that examined the relationship between exposure of children to radiographic examinations and micronucleus.

Results: A total of 17 full-text manuscripts were screened for eligibility. Only two studies found a difference in micronucleus labeling. On the other hand, all studies showed that X-ray was able to induce cellular death in oral mucosa cells. Following the parameters of the Effective Practices in Public Health Project (EPHPP), five manuscripts reached moderate and strong scores, and four studies were categorized as weak at final rating. In the meta-analysis, statistically significant difference was detected in micronucleated cells in children before and after radiographic examinations (SMD = 0.96, 95% CI, 0.07-1.84, p = .04), with τ²=1.09; χ²=53.37, and p < .001.

Conclusion: Radiographic examinations in children can cause genotoxic and cytotoxic damage in the oral epithelium with a large effect size.

Purpose: With the development of nuclear technology and radiotherapy, the risk of radiation injury has been increasing. Therefore, it is important to find an effective radiation-protective agent. In this study, we designed and synthesized a novel compound called compound 8, of which the radioprotective effect and mechanism were studied.

Materials and methods: Before being exposed to ionizing radiation, mice were pretreated with compound 8. The 30-day mortality assay, hematoxylin-eosin staining, and immunohistochemistry staining assay were performed to evaluate the anti-radiation effect of the compound 8. TUNEL and immunofluorescence assays were conducted to study the anti-radiation mechanism of compound 8.

Results: Compared to the IR + vehicle group, the 30-day survival rate of mice treated with 25 mg/kg of compound 8 was significantly improved after 8 Gy total body irradiation. In the morphological study of the small intestine, we found that compound 8 could maintain crypt-villus structures in the irradiated mice. Further immunohistochemical staining displayed that compound 8 could improve the survival of Lgr5⁺ cells, ki67⁺ cells, and lysozyme⁺ cells. The results of TUNEL and immunofluorescence assays showed that compound 8 could decrease the expression of apoptosis-related caspase-8/-9, γ-H2AX, Bax, and p53.

Conclusions: These results indicate that compound 8 exerts its effects by maintaining structure and function of small intestine. It also reduces DNA damage, promotes crypt proliferation and differentiation. Moreover, it may enhance the anti-apoptotic ability of small intestinal tissue by inhibiting the activation of p53 and blocking the caspase cascade reaction. Compound 8 can protect the intestinal tract from post-radiation damage, it is thus a new and effective protective agent of radiation.

Purpose: Five different types of synthesized azadispiro derivatives have been analyzed for radiation absorption capacity and determined their potential to be exploited as substances for a drug to be developed against radiation has been investigated.

Material and methods: Fast neutron attenuation parameters like the effective mean free path, half-value layer (HVL), removal cross-sections, and neutron transmission number were found with the Monte Carlo simulation Geometry And Tracking (GEANT4) code. Gamma radiation absorption parameters, such as effective atom number (Z_eff), mean free path (MFP), mass attenuation coefficient (MAC), and half-value layer (HVL) were theoretically determined with WinXCom software. Besides, the exposure build-up factor (EBF) was calculated by using GP fitting parameters. Neutron absorption dose rate was experimentally calculated with ²⁴¹Am-Be fast neutron source which has 4.5 MeV of energy, 74 GBq activity, and portative BF₃ neutron detector. Ames/Salmonella test systems were used for the genotoxic potentials of the azadispiro derivatives.

Results and conclusions: Experimental and theoretical results were checked with paraffin and High-Density Polyethylene. The results showed that Azadispiro derivatives have neutron radiation absorption capability close to paraffin and High-Density Polyethylene. The gamma radiation absorption properties for azadispiro derivatives have been investigated, and it has been observed that these materials can absorb gamma radiation. Ames/Salmonella assay was used to examine whether the derivatives had a genotoxic effect probability or not. The results showed that these derivatives were genotoxic and safe at test doses (up to 5 mM). Consequently, it has been understood that these azadispiro derivatives can be used as active and genotoxic safety ingredients in the production of a protective drug against both neutrons and gamma rays.

Purpose: Lung cancer is considered as one of the most frequent malignancies worldwide. Radiotherapy is the main treatment modality applied for locally advanced disease, but remnant surviving cancer tissue results in disease progression in the majority of irradiated lung carcinomas. Metabolic reprogramming is regarded as a cancer hallmark and is associated with resistance to radiation therapy. Here, we explored metabolic alterations possibly related to cancer cell radioresistance.

Materials and methods: We compared the expression of metabolism-related enzymes in the parental A549 lung cancer cell line along with two new cell lines derived from A549 cells after recovery from three (A549-IR3) and six (A549-IR6) irradiation doses with 4 Gy. Differential GLUT1 and GYS1 expression on proliferation and radioresistance were also comparatively investigated.

Results: A549-IR cells displayed increased extracellular glucose absorption, and enhanced mRNA and protein levels of the GLUT1 glucose transporter. GLUT1 inhibition with BAY-876, suppressed cell proliferation and the effect was significantly more profound on A549-IR3 cells. Protein levels of molecules associated with aerobic or anaerobic glycolysis, or the phosphate pentose pathway were similar in all three cell lines. However, glycogen synthase 1 (GYS1) was upregulated, especially in the A549-IR3 cell line, suggestive of glycogen accumulation in cells surviving post irradiation. GYS1-gene silencing repressed the proliferation capacity of A549, but this increased their radioresistance. The radio-protective effect of the suppression of proliferative activity induced by GYS1 silencing did not protect A549-IR3 cells against further irradiation.

Conclusions: These findings indicate that GYS1 activity is a critical component of the metabolism of lung cancer cells surviving after fractionated radiotherapy. Targeting the glycogen metabolic reprogramming after irradiation may be a valuable approach to pursue eradication of the post-radiotherapy remnant of disease.