Pub Date : 2024-01-01Epub Date: 2024-06-18DOI: 10.1080/09553002.2024.2369104
Susanna Salminen-Paatero, Helena Mussalo-Rauhamaa
Purpose: Plutonium and iron share a common metabolism in terms of their transportation and accumulation in the human body. This study examined their concentrations in livers with different states of health, and the effects of fatty degeneration and cirrhosis on their accumulation in the liver.
Materials and methods: We determined the concentrations of plutonium and iron in autopsy liver samples from 1976-1979. Using statistical analysis, we investigated the relationships between the different variables.
Results and conclusions: The burdens of 239,240Pu and Fe correlated positively (Rs = 0.411) in the healthy livers, but not in the livers that had pathological findings. In contrast to the Fe content, the 239,240Pu content in the fatty degenerated or cirrhotic livers was significantly lower than that in normal livers. This difference may suggest that plutonium and iron do not accumulate or are not excreted in the same way in fatty degenerated and cirrhotic livers. The reaction mechanisms for the binding and excretion of plutonium, particularly in a fatty degenerated liver, are not yet fully known.
{"title":"Effects of liver's state of health on its iron and plutonium content.","authors":"Susanna Salminen-Paatero, Helena Mussalo-Rauhamaa","doi":"10.1080/09553002.2024.2369104","DOIUrl":"10.1080/09553002.2024.2369104","url":null,"abstract":"<p><strong>Purpose: </strong>Plutonium and iron share a common metabolism in terms of their transportation and accumulation in the human body. This study examined their concentrations in livers with different states of health, and the effects of fatty degeneration and cirrhosis on their accumulation in the liver.</p><p><strong>Materials and methods: </strong>We determined the concentrations of plutonium and iron in autopsy liver samples from 1976-1979. Using statistical analysis, we investigated the relationships between the different variables.</p><p><strong>Results and conclusions: </strong>The burdens of <sup>239,240</sup>Pu and Fe correlated positively (R<sub>s</sub> = 0.411) in the healthy livers, but not in the livers that had pathological findings. In contrast to the Fe content, the <sup>239,240</sup>Pu content in the fatty degenerated or cirrhotic livers was significantly lower than that in normal livers. This difference may suggest that plutonium and iron do not accumulate or are not excreted in the same way in fatty degenerated and cirrhotic livers. The reaction mechanisms for the binding and excretion of plutonium, particularly in a fatty degenerated liver, are not yet fully known.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1165-1173"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Ionizing radiation is a harsh environmental factor that could induce plant senescence. We hypothesized that radiation-related senescence remodels proteome, particularly by triggering the accumulation of prion-like proteins in plant tissues. The object of this study, pea (Pisum sativum L.), is an agriculturally important legume. Research on the functional importance of amyloidogenic proteins was never performed on this species.
Materials and methods: Pea seeds were irradiated in the dose range 5-50 Gy of X-rays. Afterward, Fourier-transform infrared spectroscopy (FTIR) was used to investigate changes in the secondary structure of proteins in germinated 3-day-old seedlings. Specifically, we evaluated the ratio between the amide I and II peaks. Next, we performed protein staining with Congo red to compare the presence of amyloids in the samples. In parallel, we profiled the detergent-resistant proteome fraction by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS). Differentially accumulated proteins were functionally analyzed in MapMan software, and the PLAAC tool was used to predict putative prion-like proteins.
Results: We showed a reduced germination rate but higher plant height and faster appearance of reproductive organs in the irradiated at dose of 50 Gy group compared with the control; furthermore, we demonstrated more β-sheets and amyloid aggregates in the roots of stressed plants. We detected 531 proteins in detergent-resistant fraction extracted from roots, and 45 were annotated as putative prion-like proteins. Notably, 29 proteins were significantly differentially abundant between the irradiated and the control groups. These proteins belong to several functional categories: amino acid metabolism, carbohydrate metabolism, cytoskeleton organization, regulatory processes, protein biosynthesis, and RNA processing. Thus, the discovery proteomics provided deep data on novel aspects of plant stress biology.
Conclusion: Our data hinted that protein accumulation stimulated seedlings' growth as well as accelerated ontogenesis and, eventually, senescence, primarily through translation and RNA processing. The increased abundance of primary metabolism-related proteins indicates more intensive metabolic processes triggered in germinating pea seeds upon X-ray exposure. The functional role of detected putative amyloidogenic proteins should be validated in overexpression or knockout follow-up studies.
{"title":"How does ionizing radiation affect amyloidogenesis in plants?","authors":"Maryna Kryvokhyzha, Sergii Litvinov, Maksym Danchenko, Lidiia Khudolieieva, Nataliia Kutsokon, Peter Baráth, Namik Rashydov","doi":"10.1080/09553002.2024.2331126","DOIUrl":"10.1080/09553002.2024.2331126","url":null,"abstract":"<p><strong>Purpose: </strong>Ionizing radiation is a harsh environmental factor that could induce plant senescence. We hypothesized that radiation-related senescence remodels proteome, particularly by triggering the accumulation of prion-like proteins in plant tissues. The object of this study, pea (<i>Pisum sativum</i> L.), is an agriculturally important legume. Research on the functional importance of amyloidogenic proteins was never performed on this species.</p><p><strong>Materials and methods: </strong>Pea seeds were irradiated in the dose range 5-50 Gy of X-rays. Afterward, Fourier-transform infrared spectroscopy (FTIR) was used to investigate changes in the secondary structure of proteins in germinated 3-day-old seedlings. Specifically, we evaluated the ratio between the amide I and II peaks. Next, we performed protein staining with Congo red to compare the presence of amyloids in the samples. In parallel, we profiled the detergent-resistant proteome fraction by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS). Differentially accumulated proteins were functionally analyzed in MapMan software, and the PLAAC tool was used to predict putative prion-like proteins.</p><p><strong>Results: </strong>We showed a reduced germination rate but higher plant height and faster appearance of reproductive organs in the irradiated at dose of 50 Gy group compared with the control; furthermore, we demonstrated more β-sheets and amyloid aggregates in the roots of stressed plants. We detected 531 proteins in detergent-resistant fraction extracted from roots, and 45 were annotated as putative prion-like proteins. Notably, 29 proteins were significantly differentially abundant between the irradiated and the control groups. These proteins belong to several functional categories: amino acid metabolism, carbohydrate metabolism, cytoskeleton organization, regulatory processes, protein biosynthesis, and RNA processing. Thus, the discovery proteomics provided deep data on novel aspects of plant stress biology.</p><p><strong>Conclusion: </strong>Our data hinted that protein accumulation stimulated seedlings' growth as well as accelerated ontogenesis and, eventually, senescence, primarily through translation and RNA processing. The increased abundance of primary metabolism-related proteins indicates more intensive metabolic processes triggered in germinating pea seeds upon X-ray exposure. The functional role of detected putative amyloidogenic proteins should be validated in overexpression or knockout follow-up studies.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"922-933"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The effect of chronic low dose-rate radiation exposure on cancers was investigated by analyzing the data of mice experiments conducted at the Institute for Environmental Sciences (IES). This analysis focuses on the differences between malignant lymphomas and solid cancers.
Materials and methods: The analysis is conducted based on the mathematical model introduced in our previous work. The model is expanded to analyze malignant lymphomas and solid cancers separately. Using the expanded model, the effect of chronic low dose-rate radiation on malignant lymphomas and solid cancers are discussed based on their occurrences, progressions, and mortalities.
Results: Non-irradiated control group and 20 mGy/day × 400 days irradiated groups are analyzed. The analysis showed that radiation exposure shortened mean life expectancy for both malignant lymphomas and solid cancers (shorter by 89.6 days for malignant lymphomas and 149.3 days for solid cancers). For malignant lymphomas, both the occurrence and the progression are affected by radiation exposure. The mean age at which malignant lymphoma developed in mice was shortened by 32.7 days and the mean progression period was shortened by 57.3 days. The occurrence of solid cancer is also affected by radiation exposure, wherein the mean age at which solid cancer develops was shortened by 147.9 days. However, no significant change in progression period of solid cancers was seen in the analysis.
Conclusions: The analysis showed that the occurrence and mean lifespan are affected in both malignant lymphomas and solid cancers. The shortening of the progression period is only seen in malignant lymphoma, no significant change was observed in solid cancers.
{"title":"An analysis of the effects of chronic low dose-rate radiation exposure on cancer focusing on the differences among cancer types.","authors":"Tetsuhiro Kinugawa, Ignacia Braga Tanaka, Satoshi Tanaka, Yuichiro Manabe, Fuminobu Sato, Takahiro Wada","doi":"10.1080/09553002.2024.2338551","DOIUrl":"10.1080/09553002.2024.2338551","url":null,"abstract":"<p><strong>Purpose: </strong>The effect of chronic low dose-rate radiation exposure on cancers was investigated by analyzing the data of mice experiments conducted at the Institute for Environmental Sciences (IES). This analysis focuses on the differences between malignant lymphomas and solid cancers.</p><p><strong>Materials and methods: </strong>The analysis is conducted based on the mathematical model introduced in our previous work. The model is expanded to analyze malignant lymphomas and solid cancers separately. Using the expanded model, the effect of chronic low dose-rate radiation on malignant lymphomas and solid cancers are discussed based on their occurrences, progressions, and mortalities.</p><p><strong>Results: </strong>Non-irradiated control group and 20 mGy/day × 400 days irradiated groups are analyzed. The analysis showed that radiation exposure shortened mean life expectancy for both malignant lymphomas and solid cancers (shorter by 89.6 days for malignant lymphomas and 149.3 days for solid cancers). For malignant lymphomas, both the occurrence and the progression are affected by radiation exposure. The mean age at which malignant lymphoma developed in mice was shortened by 32.7 days and the mean progression period was shortened by 57.3 days. The occurrence of solid cancer is also affected by radiation exposure, wherein the mean age at which solid cancer develops was shortened by 147.9 days. However, no significant change in progression period of solid cancers was seen in the analysis.</p><p><strong>Conclusions: </strong>The analysis showed that the occurrence and mean lifespan are affected in both malignant lymphomas and solid cancers. The shortening of the progression period is only seen in malignant lymphoma, no significant change was observed in solid cancers.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"903-911"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-16DOI: 10.1080/09553002.2023.2295300
Seo Young Kwak, Ji-Hye Park, Hee-Young Won, Hyosun Jang, Seung Bum Lee, Won Il Jang, Sunhoo Park, Min-Jung Kim, Sehwan Shim
Purpose: In case of a nuclear accident, individuals with high-dose radiation exposure (>1-2 Gy) should be rapidly identified. While ferredoxin reductase (FDXR) was recently suggested as a radiation-responsive gene, the use of a single gene biomarker limits radiation dose assessment. To overcome this limitation, we sought to identify reliable radiation-responsive gene biomarkers.
Materials and methods: Peripheral blood mononuclear cells (PBMCs) were isolated from mice after total body irradiation, and gene expression was analyzed using a microarray approach to identify radiation-responsive genes.
Results: In light of the essential role of the immune response following radiation exposure, we selected several immune-related candidate genes upregulated by radiation exposure in both mouse and human PBMCs. In particular, the expression of ACOD1 and CXCL10 increased in a radiation dose-dependent manner, while remaining unchanged following lipopolysaccharide (LPS) stimulation in human PBMCs. The expression of both genes was further evaluated in the blood of cancer patients before and after radiotherapy. CXCL10 expression exhibited a distinct increase after radiotherapy and was positively correlated with FDXR expression.
Conclusions: CXCL10 expression in irradiated PBMCs represents a potential biomarker for radiation exposure.
{"title":"CXCL10 upregulation in radiation-exposed human peripheral blood mononuclear cells as a candidate biomarker for rapid triage after radiation exposure.","authors":"Seo Young Kwak, Ji-Hye Park, Hee-Young Won, Hyosun Jang, Seung Bum Lee, Won Il Jang, Sunhoo Park, Min-Jung Kim, Sehwan Shim","doi":"10.1080/09553002.2023.2295300","DOIUrl":"10.1080/09553002.2023.2295300","url":null,"abstract":"<p><strong>Purpose: </strong>In case of a nuclear accident, individuals with high-dose radiation exposure (>1-2 Gy) should be rapidly identified. While ferredoxin reductase (FDXR) was recently suggested as a radiation-responsive gene, the use of a single gene biomarker limits radiation dose assessment. To overcome this limitation, we sought to identify reliable radiation-responsive gene biomarkers.</p><p><strong>Materials and methods: </strong>Peripheral blood mononuclear cells (PBMCs) were isolated from mice after total body irradiation, and gene expression was analyzed using a microarray approach to identify radiation-responsive genes.</p><p><strong>Results: </strong>In light of the essential role of the immune response following radiation exposure, we selected several immune-related candidate genes upregulated by radiation exposure in both mouse and human PBMCs. In particular, the expression of ACOD1 and CXCL10 increased in a radiation dose-dependent manner, while remaining unchanged following lipopolysaccharide (LPS) stimulation in human PBMCs. The expression of both genes was further evaluated in the blood of cancer patients before and after radiotherapy. CXCL10 expression exhibited a distinct increase after radiotherapy and was positively correlated with FDXR expression.</p><p><strong>Conclusions: </strong>CXCL10 expression in irradiated PBMCs represents a potential biomarker for radiation exposure.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"541-549"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the short-season winter environment of India and Bangladesh, lentil growth and seed yield are significantly hindered by foliar blight caused by Stemphylium botryosum. As the international germplasm pool lacks a resistance source, the study aims to develop a mutant population to identify a high-yielding mutant resistance against the pathogen. A gamma-irradiated population was developed based on its GR50 dose of 248.8 Gy. The screening of almost 130,000 M2 plants identified a tolerant lentil mutant, MM216. The multi-location trials revealed that MM216 showed an impressive and robust resistance; the selected mutant line could be recommended as a donor in the lentil breeding program against the pathogen globally. A 100 g seed was exposed to a GR50 dose to develop the M1 population. At maturity, at least 100 M2 seeds of each 1300 M1 plant were harvested individually. So, almost 130,000 M2 plants were screened in the disease hot spot. The selected mutants were advanced to M7 by screening in the field and challenged in controlled conditions with the pure pathogen isolate. A resistance mutant, MM216, with a per cent disease index (PDI) of <10, was identified where the mean of the check varieties, WBL 77, was >55. The resistance ability was confirmed further in controlled conditions. The fungal and plant DNA ratio was almost negligible in the tolerant mutant, whereas it was 0.17 in WBL77 at 196 h post-inoculation. The selected mutant did not display any yield penalty, but there was a delay in flowering by a week compared to WBL77.
{"title":"Identification and analysis of gamma-irradiation-induced Stemphylium blight tolerant lentil (<i>Lens culinaris</i>) mutant.","authors":"Bipasha Adhikari, Anirban Roy, Hemakumar Reddy, Debarati Roy, Camellia Das, Dhriti Ghosh, Souvik Das, Suvendu Mondal, Rajib Nath, Prabir K Bhattacharyya, Sanjay K Jambulkar, Somnath Bhattacharyya","doi":"10.1080/09553002.2024.2409667","DOIUrl":"10.1080/09553002.2024.2409667","url":null,"abstract":"<p><p>In the short-season winter environment of India and Bangladesh, lentil growth and seed yield are significantly hindered by foliar blight caused by <i>Stemphylium botryosum</i>. As the international germplasm pool lacks a resistance source, the study aims to develop a mutant population to identify a high-yielding mutant resistance against the pathogen. A gamma-irradiated population was developed based on its GR50 dose of 248.8 Gy. The screening of almost 130,000 M2 plants identified a tolerant lentil mutant, MM216. The multi-location trials revealed that MM216 showed an impressive and robust resistance; the selected mutant line could be recommended as a donor in the lentil breeding program against the pathogen globally. A 100 g seed was exposed to a GR50 dose to develop the M1 population. At maturity, at least 100 M2 seeds of each 1300 M1 plant were harvested individually. So, almost 130,000 M2 plants were screened in the disease hot spot. The selected mutants were advanced to M7 by screening in the field and challenged in controlled conditions with the pure pathogen isolate. A resistance mutant, MM216, with a per cent disease index (PDI) of <10, was identified where the mean of the check varieties, WBL 77, was >55. The resistance ability was confirmed further in controlled conditions. The fungal and plant DNA ratio was almost negligible in the tolerant mutant, whereas it was 0.17 in WBL77 at 196 h post-inoculation. The selected mutant did not display any yield penalty, but there was a delay in flowering by a week compared to WBL77.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1722-1730"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-11-20DOI: 10.1080/09553002.2023.2281523
F Zölzer, T Schneider, E Ainsbury, A Goto, L Liutsko, G O'Reilly, J Lochard
Purpose: Over the last decade or so, ethical and societal aspects of radiological protection have received increasing attention. This is also reflected in the publications of the International Commission on Radiological Protection (ICRP). The current paper aims at identifying relevant ethical and societal topics which should receive attention in the context of radiological protection for offspring and next generations.
Materials and methods: We present a non-comprehensive review of the subject, based on presentation made at an ICRP workshop in Budapest in 2022. We first discuss the ethical values promoted by ICRP, and the application of these values in cases of (potential) pre-conceptual and prenatal radiation exposures. We then consider experience gained after the Fukushima accident indicating particular societal concerns about the health effects of such exposures.
Results and conclusions: Beneficence/non-maleficence, prudence, justice and dignity, the "core values" of the system of radiological protection have special roles to play when heritable and/or in utero effects are to be considered. Prudence, in particular, must be taken account of in view of the fact that solid scientific data in humans are largely lacking in this area, and it is necessary to rely on insights from animal experiments as well as theoretical considerations. As regards societal considerations, the perception of risk among (potentially) affected populations needs to be taken seriously. Accountability, transparency, and inclusivity, the "procedural values" promoted by ICRP for the practical implementation of the system of radiological protection play a central role in overcoming skepticism and creating trust. Stakeholder involvement should emphasize cooperation and dialogue, which allows for the joint evaluation of an exposure situation by experts and affected people.
{"title":"Ethical and societal aspects of radiological protection for offspring and next generations.","authors":"F Zölzer, T Schneider, E Ainsbury, A Goto, L Liutsko, G O'Reilly, J Lochard","doi":"10.1080/09553002.2023.2281523","DOIUrl":"10.1080/09553002.2023.2281523","url":null,"abstract":"<p><strong>Purpose: </strong>Over the last decade or so, ethical and societal aspects of radiological protection have received increasing attention. This is also reflected in the publications of the International Commission on Radiological Protection (ICRP). The current paper aims at identifying relevant ethical and societal topics which should receive attention in the context of radiological protection for offspring and next generations.</p><p><strong>Materials and methods: </strong>We present a non-comprehensive review of the subject, based on presentation made at an ICRP workshop in Budapest in 2022. We first discuss the ethical values promoted by ICRP, and the application of these values in cases of (potential) pre-conceptual and prenatal radiation exposures. We then consider experience gained after the Fukushima accident indicating particular societal concerns about the health effects of such exposures.</p><p><strong>Results and conclusions: </strong>Beneficence/non-maleficence, prudence, justice and dignity, the \"core values\" of the system of radiological protection have special roles to play when heritable and/or in utero effects are to be considered. Prudence, in particular, must be taken account of in view of the fact that solid scientific data in humans are largely lacking in this area, and it is necessary to rely on insights from animal experiments as well as theoretical considerations. As regards societal considerations, the perception of risk among (potentially) affected populations needs to be taken seriously. Accountability, transparency, and inclusivity, the \"procedural values\" promoted by ICRP for the practical implementation of the system of radiological protection play a central role in overcoming skepticism and creating trust. Stakeholder involvement should emphasize cooperation and dialogue, which allows for the joint evaluation of an exposure situation by experts and affected people.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1371-1381"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-07-26DOI: 10.1080/09553002.2024.2373752
Aleksandra M Ristić Fira, Otilija D Keta, Vladana D Petković, Miloš Đorđević, Giada Petringa, Serena Fattori, Roberto Catalano, Giuseppe Pablo Cirrone, Giacomo Cuttone, Dousatsu Sakata, Ngoc Hoang Tran, Konstantinos Chatzipapas, Sebastien Incerti, Ivan M Petrović
Purpose: Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET).
Materials and methods: The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci.
Results: With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines.
Conclusion: Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.
目的:基于对扩大氦离子照射抗放射细胞实验数据库的浓厚兴趣,HTB140、MCF-7和HTB177人类恶性细胞暴露于不同线性能量转移(LET)的氦离子束:细胞沿扩大的 62 MeV/u 氦离子布拉格峰照射,LET 分别为 4.9、9.8、23.4 和 36.8 keV/µm。实验设计采用 Geant4 工具包进行数值模拟。对细胞存活率进行评估,并与参考γ射线进行比较。通过γ-H2AX病灶评估DNA双链断裂情况:结果:随着 LET 的增加,2 Gy 存活率下降,而 RBE(2 Gy,γ)逐渐增加。对于 HTB140 细胞,当剂量超过 4 Gy 时,存活率出现轻微饱和,而 RBE(2 Gy,γ)的增加不受影响。随着 LET 的增加,γ-H2AX 病灶在照射后 0.5 h 出现增加。在相同的 LET 下,不同细胞系的病灶数量没有明显差异。从 0.5 到 24 小时,病灶数量下降到残余水平。在每个时间点,三种细胞系之间的 DNA DSB 差异很小:对不同LET的氦离子照射三种细胞系所获得的数据进行分析后发现,与γ射线相比,氦离子具有较高的消除能力,并能产生大量DNA DSB,介于质子和碳离子之间。
{"title":"In vitro validation of helium ion irradiations as a function of linear energy transfer in radioresistant human malignant cells.","authors":"Aleksandra M Ristić Fira, Otilija D Keta, Vladana D Petković, Miloš Đorđević, Giada Petringa, Serena Fattori, Roberto Catalano, Giuseppe Pablo Cirrone, Giacomo Cuttone, Dousatsu Sakata, Ngoc Hoang Tran, Konstantinos Chatzipapas, Sebastien Incerti, Ivan M Petrović","doi":"10.1080/09553002.2024.2373752","DOIUrl":"10.1080/09553002.2024.2373752","url":null,"abstract":"<p><strong>Purpose: </strong>Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET).</p><p><strong>Materials and methods: </strong>The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci.</p><p><strong>Results: </strong>With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines.</p><p><strong>Conclusion: </strong>Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1426-1437"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-08-05DOI: 10.1080/09553002.2024.2374903
Tianying Liu, Qing Xie, Wenli Wang
Background: Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation.
Methods: Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry.
Results: USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models.
Conclusion: In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.
{"title":"Ultrasound-stimulated microbubbles enhances radiosensitivity in cervical cancer.","authors":"Tianying Liu, Qing Xie, Wenli Wang","doi":"10.1080/09553002.2024.2374903","DOIUrl":"10.1080/09553002.2024.2374903","url":null,"abstract":"<p><strong>Background: </strong>Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation.</p><p><strong>Methods: </strong>Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry.</p><p><strong>Results: </strong>USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models.</p><p><strong>Conclusion: </strong>In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1416-1425"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-05DOI: 10.1080/09553002.2023.2295293
Stéphane Grison, Ignacia Iii Braga-Tanaka, Sarah Baatout, Dmitry Klokov
Purpose: The radiation protection community has been particularly attentive to the risks of delayed effects on offspring from low dose or low dose-rate exposures to ionizing radiation. Despite this, the current epidemiologic studies and scientific data are still insufficient to provide the necessary evidence for improving risk assessment guidelines. This literature review aims to inform future studies on multigenerational and transgenerational effects. It primarily focuses on animal studies involving in utero exposure and discusses crucial elements for interpreting the results. These elements include in utero exposure scenarios relative to the developmental stages of the embryo/fetus, and the primary biological mechanisms responsible for transmitting heritable or hereditary effects to future generations. The review addresses several issues within the contexts of both multigenerational and transgenerational effects, with a focus on hereditary perspectives.
Conclusions: Knowledge consolidation in the field of Developmental Origins of Health and Disease (DOHaD) has led us to propose a new study strategy. This strategy aims to address the transgenerational effects of in utero exposure to low dose and low dose-rate radiation. Within this concept, there is a possibility that disruption of epigenetic programming in embryonic and fetal cells may occur. This disruption could lead to metabolic dysfunction, which in turn may cause abnormal responses to future environmental challenges, consequently increasing disease risk. Lastly, we discuss methodological limitations in our studies. These limitations are related to cohort size, follow-up time, model radiosensitivity, and analytical techniques. We propose scientific and analytical strategies for future research in this field.
{"title":"<i>In utero</i> exposure to ionizing radiation and metabolic regulation: perspectives for future multi- and trans-generation effects studies.","authors":"Stéphane Grison, Ignacia Iii Braga-Tanaka, Sarah Baatout, Dmitry Klokov","doi":"10.1080/09553002.2023.2295293","DOIUrl":"10.1080/09553002.2023.2295293","url":null,"abstract":"<p><strong>Purpose: </strong>The radiation protection community has been particularly attentive to the risks of delayed effects on offspring from low dose or low dose-rate exposures to ionizing radiation. Despite this, the current epidemiologic studies and scientific data are still insufficient to provide the necessary evidence for improving risk assessment guidelines. This literature review aims to inform future studies on multigenerational and transgenerational effects. It primarily focuses on animal studies involving <i>in utero</i> exposure and discusses crucial elements for interpreting the results. These elements include <i>in utero</i> exposure scenarios relative to the developmental stages of the embryo/fetus, and the primary biological mechanisms responsible for transmitting heritable or hereditary effects to future generations. The review addresses several issues within the contexts of both multigenerational and transgenerational effects, with a focus on hereditary perspectives.</p><p><strong>Conclusions: </strong>Knowledge consolidation in the field of Developmental Origins of Health and Disease (DOHaD) has led us to propose a new study strategy. This strategy aims to address the transgenerational effects of <i>in utero</i> exposure to low dose and low dose-rate radiation. Within this concept, there is a possibility that disruption of epigenetic programming in embryonic and fetal cells may occur. This disruption could lead to metabolic dysfunction, which in turn may cause abnormal responses to future environmental challenges, consequently increasing disease risk. Lastly, we discuss methodological limitations in our studies. These limitations are related to cohort size, follow-up time, model radiosensitivity, and analytical techniques. We propose scientific and analytical strategies for future research in this field.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1283-1296"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139099429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: In this paper, we described our mathematical model for radiation-induced life shortening in detail and applied the model to the experimental data on mice to investigate the effect of radiation on cancer-related life-shortening.
Materials and methods: Our mathematical model incorporates the following components: (i) occurrence of cancer, (ii) progression of cancer over time, and (iii) death from cancer. We evaluated the progression of cancer over time by analyzing the cancer incidence data and cumulative mortalities data obtained from mice experiments conducted at the Institute for Environmental Sciences (IES).
Results: We analyzed non-irradiated control and 20 mGy/day × 400 days irradiated groups. In the analysis, all malignant neoplasms were lumped together and referred to as 'cancer'. Our analysis showed that the reduction in lifespan (104 days in median) was the result of the early onset of cancer (68 days in median) and the shortening of the cancer progression period (48 days in median).
Conclusions: We described in detail our mathematical model for radiation-induced life-shortening attributed to cancer. We analyzed the mice data obtained from the experiment conducted at the IES using our model. We decomposed radiation-induced life-shortening into the early onset of cancer and the shortening of the cancer progression period.
{"title":"A mathematical model for radiation-induced life-shortening attributed to cancer.","authors":"Tetsuhiro Kinugawa, Ignacia Braga Tanaka, Satoshi Tanaka, Yuichiro Manabe, Fuminobu Sato, Takahiro Wada","doi":"10.1080/09553002.2023.2261529","DOIUrl":"10.1080/09553002.2023.2261529","url":null,"abstract":"<p><strong>Purpose: </strong>In this paper, we described our mathematical model for radiation-induced life shortening in detail and applied the model to the experimental data on mice to investigate the effect of radiation on cancer-related life-shortening.</p><p><strong>Materials and methods: </strong>Our mathematical model incorporates the following components: (i) occurrence of cancer, (ii) progression of cancer over time, and (iii) death from cancer. We evaluated the progression of cancer over time by analyzing the cancer incidence data and cumulative mortalities data obtained from mice experiments conducted at the Institute for Environmental Sciences (IES).</p><p><strong>Results: </strong>We analyzed non-irradiated control and 20 mGy/day × 400 days irradiated groups. In the analysis, all malignant neoplasms were lumped together and referred to as 'cancer'. Our analysis showed that the reduction in lifespan (104 days in median) was the result of the early onset of cancer (68 days in median) and the shortening of the cancer progression period (48 days in median).</p><p><strong>Conclusions: </strong>We described in detail our mathematical model for radiation-induced life-shortening attributed to cancer. We analyzed the mice data obtained from the experiment conducted at the IES using our model. We decomposed radiation-induced life-shortening into the early onset of cancer and the shortening of the cancer progression period.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"176-182"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}