International Journal of Radiation Biology最新文献

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Multiple levels of stochasticity accounted for in different radiation biophysical models: from physics to biology. 在不同的辐射生物物理模型中考虑了多重水平的随机性:从物理学到生物学。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 DOI: 10.1080/09553002.2023.2146230
Francesco G Cordoni, Marta Missiaggia, Chiara La Tessa, Emanuele Scifoni
{"title":"Multiple levels of stochasticity accounted for in different radiation biophysical models: from physics to biology.","authors":"Francesco G Cordoni,&nbsp;Marta Missiaggia,&nbsp;Chiara La Tessa,&nbsp;Emanuele Scifoni","doi":"10.1080/09553002.2023.2146230","DOIUrl":"https://doi.org/10.1080/09553002.2023.2146230","url":null,"abstract":"<p><strong>Purpose: </strong>In the present paper we investigate how some stochastic effects are included in a class of radiobiological models with particular emphasis on how such randomnesses reflect into the predicted cell survival curve.</p><p><strong>Materials and methods: </strong>We consider four different models, namely the <i>Generalized Stochastic Microdosimetric Model</i> GSM<sup>2</sup>, in its original full form, the <i>Dirac</i> GSM<sup>2</sup> the <i>Poisson</i> GSM<sup>2</sup><math></math> and the <i>Repair-Misrepair Model</i> (RMR). While GSM<sup>2</sup><math></math> and the RMR models are known in literature, the Dirac and the Poisson GSM<sup>2</sup><math><mi> </mi></math> have been newly introduced in this work. We further numerically investigate via Monte Carlo simulation of four different particle beams, how the proposed stochastic approximations reflect into the predicted survival curves. To achieve these results, we consider different ion species at energies of interest for therapeutic applications, also including a mixed field scenario.</p><p><strong>Results: </strong>We show how the <i>Dirac</i> GSM<sup>2</sup><math><mo>,</mo></math> the <i>Poisson</i> GSM<sup>2</sup><math></math> and the RMR can be obtained from the GSM<sup>2</sup><math></math> under suitable approximations on the stochasticity considered. We analytically derive the cell survival curve predicted by the four models, characterizing rigorously the high and low dose limits. We further study how the theoretical findings emerge also using Monte Carlo numerical simulations.</p><p><strong>Conclusions: </strong>We show how different models include different levels of stochasticity in the description of cellular response to radiation. This translates into different cell survival predictions depending on the radiation quality.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 5","pages":"807-822"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Therapeutic efficacy of cyclin-dependent kinase inhibition in combination with ionizing radiation for lung cancer. 细胞周期依赖性激酶抑制联合电离辐射治疗癌症的疗效。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 Epub Date: 2023-01-04 DOI: 10.1080/09553002.2023.2161658
Jenny Ling-Yu Chen, Chun-Kai Pan, Li-Cheng Lin, Ching-Yi Tsai, Ching-Ying Kuo, Yu-Sen Huang, Yu-Li Lin
{"title":"Therapeutic efficacy of cyclin-dependent kinase inhibition in combination with ionizing radiation for lung cancer.","authors":"Jenny Ling-Yu Chen,&nbsp;Chun-Kai Pan,&nbsp;Li-Cheng Lin,&nbsp;Ching-Yi Tsai,&nbsp;Ching-Ying Kuo,&nbsp;Yu-Sen Huang,&nbsp;Yu-Li Lin","doi":"10.1080/09553002.2023.2161658","DOIUrl":"10.1080/09553002.2023.2161658","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the therapeutic efficacy of cyclin-dependent kinase (CDK) inhibition in combination with ionizing radiation for lung cancer.</p><p><strong>Materials and methods: </strong>Human lung adenocarcinoma (A549) and squamous cell carcinoma (H520) cells were used to evaluate the therapeutic efficacy of CDK inhibition in combination with ionizing radiation in vitro using colony formation assay, γH2AX immunofluorescence staining, western blotting, and cell cycle phase analysis. We also performed in vivo evaluations of ectopic tumor growth.</p><p><strong>Results: </strong>In vitro pretreatment with the CDK inhibitor, seliciclib, before irradiation significantly decreased the survival of A549 and H520 cells in a dose-dependent manner. Although CDK inhibition alone did not increase the intensity of γH2AX foci, its combination with ionizing radiation increased DNA double-strand breaks, as shown by γH2AX immunofluorescence staining and western blotting. The combination of CDK inhibition and ionizing radiation-induced G2/M arrest and increased apoptosis, as evidenced by the increased proportion of cells in G2/M arrest, subG1 apoptotic population, and expression of apoptotic markers (cleaved PARP-1 and cleaved caspase-3). Mechanistic studies showed reduced expression of cyclin A with combined treatment, indicating cell cycle shifting effects. An in vivo xenograft model showed that the combination of CDK inhibition and ionizing radiation delayed xenograft tumor growth, and increased the proportion of cleaved PARP-1- and cleaved caspase-3-positive cells, compared to either treatment alone.</p><p><strong>Conclusions: </strong>We provide preclinical tumoricidal evidence that the combination of CDK inhibition and ionizing radiation is an efficacious treatment for lung cancer.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 8","pages":"1257-1266"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9907968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine intelligence for radiation science: summary of the Radiation Research Society 67th annual meeting symposium. 辐射科学的机器智能:辐射研究学会第67届年会研讨会纪要。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 DOI: 10.1080/09553002.2023.2173823
Lydia J Wilson, Frederico C Kiffer, Daniel C Berrios, Abigail Bryce-Atkinson, Sylvain V Costes, Olivier Gevaert, Bruno F E Matarèse, Jack Miller, Pritam Mukherjee, Kristen Peach, Paul N Schofield, Luke T Slater, Britta Langen
{"title":"Machine intelligence for radiation science: summary of the Radiation Research Society 67th annual meeting symposium.","authors":"Lydia J Wilson,&nbsp;Frederico C Kiffer,&nbsp;Daniel C Berrios,&nbsp;Abigail Bryce-Atkinson,&nbsp;Sylvain V Costes,&nbsp;Olivier Gevaert,&nbsp;Bruno F E Matarèse,&nbsp;Jack Miller,&nbsp;Pritam Mukherjee,&nbsp;Kristen Peach,&nbsp;Paul N Schofield,&nbsp;Luke T Slater,&nbsp;Britta Langen","doi":"10.1080/09553002.2023.2173823","DOIUrl":"https://doi.org/10.1080/09553002.2023.2173823","url":null,"abstract":"<p><p>The era of high-throughput techniques created big data in the medical field and research disciplines. Machine intelligence (MI) approaches can overcome critical limitations on how those large-scale data sets are processed, analyzed, and interpreted. The 67<sup>th</sup> Annual Meeting of the Radiation Research Society featured a symposium on MI approaches to highlight recent advancements in the radiation sciences and their clinical applications. This article summarizes three of those presentations regarding recent developments for metadata processing and ontological formalization, data mining for radiation outcomes in pediatric oncology, and imaging in lung cancer.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 8","pages":"1291-1300"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural study of wild-type and phospho-mimic XRCC4 dimer and multimer proteins using circular dichroism spectroscopy. 使用圆二色光谱法对野生型和磷酸模拟XRCC4二聚体和多聚体蛋白的结构研究。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 Epub Date: 2023-06-01 DOI: 10.1080/09553002.2023.2214210
Kai Nishikubo, Maho Hasegawa, Yudai Izumi, Kentaro Fujii, Koichi Matsuo, Yoshihisa Matsumoto, Akinari Yokoya
{"title":"Structural study of wild-type and phospho-mimic XRCC4 dimer and multimer proteins using circular dichroism spectroscopy.","authors":"Kai Nishikubo,&nbsp;Maho Hasegawa,&nbsp;Yudai Izumi,&nbsp;Kentaro Fujii,&nbsp;Koichi Matsuo,&nbsp;Yoshihisa Matsumoto,&nbsp;Akinari Yokoya","doi":"10.1080/09553002.2023.2214210","DOIUrl":"10.1080/09553002.2023.2214210","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the structural features of wild-type and phospho-mimicking mutated XRCC4 protein, a protein involved in DNA double-strand break repair.</p><p><strong>Materials and methods: </strong>XRCC4 with a HisTag were expressed by <i>E. coli</i> harboring plasmid DNA and purified. Phospho-mimicking mutants in which one phosphorylation site was replaced with aspartic acid were also prepared in order to reproduce the negative charge resulting from phosphorylation. The proteins were separated into dimers and multimers by gel filtration chromatography. Circular dichroism (CD) spectroscopy was performed in the region from ultraviolet to vacuum-ultraviolet. The CD spectra were analyzed with two analysis programs to evaluate the secondary structures of the wild-type and phospho-mimicked dimers and multimers.</p><p><strong>Result and discussion: </strong>The proportion of β-strand in the wild-type dimers was very low, particularly in their C-terminal region, including the five phosphorylation sites. The secondary structure of the phospho-mimic hardly changed in the dimeric form. In contrast, the β-strand content increased and the α-helix content decreased upon multimerization of the wild-type protein. The structural change of multimers slightly depended on the phospho-mimic site. These results suggest that the β-strand structure stabilizes the multimerization of XRCC4 and it is regulated by phosphorylation at the C-terminal site in living cells.</p><p><strong>Conclusion: </strong>An increase in the β-strand content in XRCC4 is essential for stabilization of the multimeric form through C-terminal phosphorylation, allowing the formation of the large double-strand break repair machinery.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":" ","pages":"1684-1691"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9931782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microarray analysis of hub genes, non-coding RNAs and pathways in lung after whole body irradiation in a mouse model. 小鼠模型全身照射后肺部中枢基因、非编码RNA和通路的微阵列分析。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 Epub Date: 2023-06-01 DOI: 10.1080/09553002.2023.2214205
Molykutty J Aryankalayil, Michelle A Bylicky, Shannon Martello, Sunita Chopra, Mary Sproull, Jared M May, Aman Shankardass, Laurel MacMillan, Claire Vanpouille-Box, Iris Eke, Kevin M K Scott, Juan Dalo, C Norman Coleman
{"title":"Microarray analysis of hub genes, non-coding RNAs and pathways in lung after whole body irradiation in a mouse model.","authors":"Molykutty J Aryankalayil, Michelle A Bylicky, Shannon Martello, Sunita Chopra, Mary Sproull, Jared M May, Aman Shankardass, Laurel MacMillan, Claire Vanpouille-Box, Iris Eke, Kevin M K Scott, Juan Dalo, C Norman Coleman","doi":"10.1080/09553002.2023.2214205","DOIUrl":"10.1080/09553002.2023.2214205","url":null,"abstract":"<p><strong>Purpose: </strong>Previous research has highlighted the impact of radiation damage, with cancer patients developing acute disorders including radiation induced pneumonitis or chronic disorders including pulmonary fibrosis months after radiation therapy ends. We sought to discover biomarkers that predict these injuries and develop treatments that mitigate this damage and improve quality of life.</p><p><strong>Materials and methods: </strong>Six- to eight-week-old female C57BL/6 mice received 1, 2, 4, 8, 12 Gy or sham whole body irradiation. Animals were euthanized 48 h post exposure and lungs removed, snap frozen and underwent RNA isolation. Microarray analysis was performed to determine dysregulation of messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA) after radiation injury.</p><p><strong>Results: </strong>We observed sustained dysregulation of specific RNA markers including: mRNAs, lncRNAs, and miRNAs across all doses. We also identified significantly upregulated genes that can indicate high dose exposure, including <i>Cpt1c, Pdk4, Gdf15</i>, and <i>Eda2r</i>, which are markers of senescence and fibrosis. Only three miRNAs were significantly dysregulated across all radiation doses: miRNA-142-3p and miRNA-142-5p were downregulated and miRNA-34a-5p was upregulated. IPA analysis predicted inhibition of several molecular pathways with increasing doses of radiation, including: T cell development, Quantity of leukocytes, Quantity of lymphocytes, and Cell viability.</p><p><strong>Conclusions: </strong>These RNA biomarkers might be highly relevant in the development of treatments and in predicting normal tissue injury in patients undergoing radiation treatment. We are conducting further experiments in our laboratory, which includes a human lung-on-a-chip model, to develop a decision tree model using RNA biomarkers.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":" ","pages":"1702-1715"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9946137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The need for consensus guidelines to address the mixed legacy of genetic damage assessments for radiofrequency fields. 需要协商一致的指导方针,以解决射频场遗传损害评估的混合遗留问题。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 DOI: 10.1080/09553002.2023.2188936
Vijayalaxmi, Kenneth R Foster
{"title":"The need for consensus guidelines to address the mixed legacy of genetic damage assessments for radiofrequency fields.","authors":"Vijayalaxmi,&nbsp;Kenneth R Foster","doi":"10.1080/09553002.2023.2188936","DOIUrl":"https://doi.org/10.1080/09553002.2023.2188936","url":null,"abstract":"<p><strong>Purpose: </strong>This review considers issues related to interpreting the mixed legacy of >300 papers published during the past three decades on possible genotoxic effects of exposure of human and animal tissues to radiofrequency electromagnetic fields (RF-EMF). The main paper reviews the evolution of consensus guidelines for genotoxicity testing and the increasing emphasis on systematic reviews for evaluation of scientific studies for use in health risk assessments. An Appendix considers some issues in assessing the bioeffects literature by examining a subset of genotoxicity publications that employed the comet assay. While most studies found no statistically significant effects of exposure, a significant minority of studies (chiefly, <i>in vivo</i> studies) reported statistically significant effects of exposure. The quality of the studies was highly variable; while several studies were meticulously done and documented, none of these studies were compliant with currently accepted guidelines such as those of the Organization for Economic Cooperation and Development (OECD). Evaluation of the studies using risk of bias (RoB) criteria showed that, in this sample of studies, higher quality studies were less likely to find statistically significant results than those of lower quality.</p><p><strong>Conclusion: </strong>The authors conclude that statistical significance should be only one consideration in evaluation of bioeffects studies. Simply listing 'statistically' significant effects identified using null hypothesis testing and the criterion <i>p</i> < 0.05 for statistical significance is misleading and uninformative in assessing health risks of exposure. A careful synthesis of evidence is needed, including assessment of study validity, biological significance of reported effects, and coherence of study results with those of other related studies.The authors recommend that all future RF genotoxicity studies intended for use in human health risk assessments and evaluations of the literature should be done in compliance with accepted quality guidelines, i.e. OECD or equivalent guidelines for genotoxicity screening studies and PRISMA or other accepted guideline for reviews of the literature. The positive studies in this group should be redone with tighter quality control to establish the reliability of the findings.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 7","pages":"1016-1026"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10087229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dose reconstruction for plutonium-239 intakes at the Rocky Flats Plant. Rocky Flats核电站钚-239入口的剂量重建。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 Epub Date: 2023-08-14 DOI: 10.1080/09553002.2023.2241896
Caleigh Samuels, Rich Leggett
{"title":"Dose reconstruction for plutonium-239 intakes at the Rocky Flats Plant.","authors":"Caleigh Samuels, Rich Leggett","doi":"10.1080/09553002.2023.2241896","DOIUrl":"10.1080/09553002.2023.2241896","url":null,"abstract":"<p><strong>Purpose: </strong>The Rocky Flats (RF) Plant was a weapons manufacturing facility that operated from the early 1950s to 1989. Its primary missions were the production of plutonium (Pu) pits for thermonuclear weapons and the processing of retired weapons for Pu recovery. The purpose of this study was to estimate radiation doses to a cohort of 4499 RF workers from an intake of <sup>239</sup>Pu, the primary plutonium isotope handled at the site.</p><p><strong>Materials and methods: </strong>The latest biokinetic models of the International Commission on Radiological Protection, or site-specific variations of those models, were used to estimate <sup>239</sup>Pu intakes for each worker based on model fits to bioassay data often coupled with lung measurements.</p><p><strong>Results: </strong>Urinary excretion and lung retention data for most <sup>239</sup>Pu intakes could be fit reasonably well by a mixture of Pu dioxide and moderately soluble material. For some workers, better fits were obtained by application of other absorption types including Type S, <sup>239</sup>Pu nitrate, or pure <sup>239</sup>Pu dioxide, or by assuming intake via a wound. The lungs typically received the highest tissue doses, with fifty-year committed equivalent doses in the range of 0.5-1 Sv for 275 workers, 1-5 Sv for 115 workers, and greater than 5 Sv for 12 workers.</p><p><strong>Conclusions: </strong>RF was a unique site regarding a large number of lung measurements available for determining the appropriate absorption types for inhaled material. This provided higher confidence in reconstructed <sup>239</sup>Pu doses than is generally gained from urinary data alone.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":" ","pages":"1841-1852"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10349339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comet Assay analysis of DNA strand breaks after exposure to the DNA-incorporated Auger Electron Emitter Iodine-125. 暴露于含DNA的俄歇电子发射器碘-125后DNA链断裂的彗星分析。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 DOI: 10.1080/09553002.2020.1851059
Marcus Unverricht-Yeboah, Kathrin Holtmann, Ralf Kriehuber
{"title":"Comet Assay analysis of DNA strand breaks after exposure to the DNA-incorporated Auger Electron Emitter Iodine-125.","authors":"Marcus Unverricht-Yeboah,&nbsp;Kathrin Holtmann,&nbsp;Ralf Kriehuber","doi":"10.1080/09553002.2020.1851059","DOIUrl":"https://doi.org/10.1080/09553002.2020.1851059","url":null,"abstract":"<p><strong>Purpose: </strong>Ionizing radiation causes various types of DNA damage e.g. single strand breaks (SSB) and double strand breaks (DSB), whereby the SSB/DSB ratio is shifted toward the DSB with increasing LET. For the DNA-incorporated Auger electron emitter Iodine-125 a SSB/DSB ratio of 5.4:1 is calculated based on computer simulations. In the presented work the SSB/DSB ratio of DNA-incorporated Iodine-125 was experimentally determined and compared to external homogenous γ-irradiation.</p><p><strong>Materials and methods: </strong>Iodine-125-iododeoxyuridine (I-125-UdR) was incorporated into the DNA of SCL-II cells and cells were subsequently frozen for decay accumulation. Accordingly, external γ-irradiation (Cs-137) experiments were performed in frozen cells. After exposure the neutral or alkaline Comet Assay was performed to quantify DSB or DSB and SSB, respectively. Automated quantification of the comets was performed using the Olive Tail Moment (Metafer CometScan; MetaSystems). Calculation of absorbed dose for Auger electrons on cellular level is extremely biased due to the exclusive DNA localization of I-125-UdR. To avoid dose calculation the γ-H2AX assay was used in order to allow the comparison of the Comet Assay data between both investigated radiation qualities.</p><p><strong>Results: </strong>For low-LET γ-radiation, a SSB/DSB ratio of 10:1 was determined. In contrast, a lower SSB/DSB ratio of 6:1 was induced by DNA-incorporated Iodine-125 which compares very well to the calculated values of Pomplun and co-authors.</p><p><strong>Conclusion: </strong>DNA-incorporated Iodine-125 induces a high-LET type DNA damage pattern in respect to SSB/DSB ratio.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 1","pages":"64-69"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/09553002.2020.1851059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10715817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Combination of PAKs inhibitors IPA-3 and PF-3758309 effectively suppresses colon carcinoma cell growth by perturbing DNA damage response. PAKs抑制剂IPA-3和PF-3758309联合使用可通过干扰DNA损伤反应有效抑制结肠癌细胞生长。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 DOI: 10.1080/09553002.2022.2110326
Muzaffer Dukel, Kayahan Fiskin
{"title":"Combination of PAKs inhibitors IPA-3 and PF-3758309 effectively suppresses colon carcinoma cell growth by perturbing DNA damage response.","authors":"Muzaffer Dukel,&nbsp;Kayahan Fiskin","doi":"10.1080/09553002.2022.2110326","DOIUrl":"https://doi.org/10.1080/09553002.2022.2110326","url":null,"abstract":"<p><strong>Purpose: </strong>PAKs proteins are speculated as new promising targets for cancer therapy due to their central role in many oncogenic pathways. Because PAKs proteins are very significant during carcinogenesis, we aimed to investigate the hypothesis that inhibition of PAKs with IPA-3 and PF-3758309 treatment could synergistically reduce colon carcinoma cell growth.</p><p><strong>Materials and methods: </strong>The cytotoxic effects of both drugs were determined by a cell viability assay. Cell cycle and apoptosis were analyzed by flow cytometry. The effects of inhibitor drugs on marker genes of apoptosis, autophagy, cell cycle, and DNA damage were tested via immunoblotting.</p><p><strong>Results and conclusions: </strong>We found out the synergistic effect of these drugs in pair on five colon cancer cell lines. Combined treatment with IPA-3+PF-3758309 in SW620 and Colo 205 cells markedly suppressed colon formation and induced apoptosis, cell cycle arrest, and autophagy compared with treatment with each drug alone. Additionally, this combination sensitized colon cancer cells to ionizing radiation that resulted in inhibition of cell growth.</p><p><strong>Significance: </strong>Collectively, our findings show for the first time that cotreatment of IPA-3 with PF-3758309 exhibits superior inhibitory effects on colon carcinoma cell growth via inducing DNA damage-related cell death and also enforces a cell cycle arrest.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":"99 2","pages":"340-354"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10785186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Determination of toxicity and radioprotective properties of bacterial and fungal eumelanin pigments. 细菌和真菌真黑色素的毒性和辐射防护特性的测定。
IF 2.6 4区 医学
International Journal of Radiation Biology Pub Date : 2023-01-01 Epub Date: 2023-04-27 DOI: 10.1080/09553002.2023.2204957
Sinan Bayram, Bünyamin Aygün, Mehmet Karadayi, Burak Alaylar, Medine Güllüce, Abdulhalik Karabulut
{"title":"Determination of toxicity and radioprotective properties of bacterial and fungal eumelanin pigments.","authors":"Sinan Bayram,&nbsp;Bünyamin Aygün,&nbsp;Mehmet Karadayi,&nbsp;Burak Alaylar,&nbsp;Medine Güllüce,&nbsp;Abdulhalik Karabulut","doi":"10.1080/09553002.2023.2204957","DOIUrl":"10.1080/09553002.2023.2204957","url":null,"abstract":"<p><strong>Purpose: </strong>Determination of the protective property of melanin, an organic polymer class consisting of phenolic and/or indolic compounds isolated from bacteria and fungi, against fast neutron radiation. To show that these melanin samples, which also have antioxidant and metal chelating properties, can be used as an active ingredient for a drug to be developed against neutrons used in nuclear research and medicine.</p><p><strong>Materials and methods: </strong>Bacterial and fungal media were prepared, and melanin pigments were produced and isolated. For molecular characterization of pigments, bacterial genomic DNA extraction, 16S rDNA gene amplification processes, and fungal genomic DNA extraction, ITS1, and ITS4 Gene Regions amplification were performed. The DEL assay was implemented to determine the genotoxicity properties of bacterial and fungal melanin pigments. Samples were prepared in a pad measuring 10 ml volume (60 × 15 mm) at a concentration of 0.2-1 microgram in 1% agarose gel for radiation-absorbed dose measurements. Absorption measurements were made using <sup>241</sup>Am-Be fast neutron source and Canberra brand NP series BF<sub>3</sub> gaseous detector to determine the neutron radiation absorption capacity of all samples. The results obtained to determine the absorption degrees of melanin samples were compared with paraffin and normal concrete, which are widely used in neutron radiation shielding studies.</p><p><strong>Results: </strong>Melanin pigments were obtained using different bacteria and fungi strains. Afterwards, the fast neutron radiation absorption capacity of these purified pigments were determined. Compared to reference samples, these pigments were found to have slightly lower radiation absorbing ability. In addition to these experiments, cytotoxicity tests were carried out using the Yeast DEL assay technique to evaluate the potential for use of these organic pigments in fields such as medicine and pharmacology. According to the results obtained from the tests, it was determined that these melanin samples did not have any toxic effects.</p><p><strong>Conclusion: </strong>It was determined that these melanin samples have the potential to be used as a radioprotective drug active substance to protect the tissues and cells of people exposed to neutron radiation after a nuclear accident or nuclear war.Giving a drug that will be developed by using these active ingredients before or after people are exposed to a radiation environment can provide great benefits.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":" ","pages":"1785-1793"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9413244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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