Purpose: The genus Mentha spp. is an aromatic herb from the family 'Lamiaceae'. It is extensively predominant in temperate and sub-temperate regions of the world. The essential oil of this species is enriched with broad aroma constituents extensively utilized in food, beverages, flavor, cosmetics, perfumery, and pharmaceutical enterprises. With the global menthol market size estimated to be worth USD 765 million in 2022, India (accompanied by China and Brazil) is the world's primary manufacturer, consumer, and exporter of Mentha oil. Despite prominent global demand, the crucial bottleneck in mint cultivation is the need for more superior commercial cultivars. Predominant vegetative propagation mode with difficulties in manual emasculation, differential blooming times, sterile/sub-sterile hybrids, and low seed viability are the primary containment in creating genetic variability by classical breeding approaches. Therefore, genetic complications encountered in conventional breeding have led the breeders to apply mutation breeding as an alternative crop improvement approach in Mentha spp. These attempts at mutation breeding have produced some distinctive mutants as genetic pools for plant breeding programs, and some novel mutant mint cultivars have been made available for commercial cultivation.
Conclusions: The prime strategy in mutation-based breeding has proven an adept means of encouraging the expression of recessive genes and producing new genetic variations. The present review comprises a significant contribution of mutation breeding approaches in the development of mutant mint species and its effects on physiological variation, photosynthetic pigment, essential oil content and composition, phytochemical-mediated defense response, pathogen resistivity, and differential expression of genes related to terpenoid biogenesis. Development and diversification have led to the release of varieties, namely Todd's Mitcham, Murray Mitcham, Pranjal, Tushar, and Kukrail in M. piperita L., Mukta, and Pratik in M. cardiaca Baker, Neera in M. spicata L., Kiran in M. citrata Ehrh., and Rose mint in M. arvensis L. that have revolutionized and uplifted mint cultivation leading to economic gain by the farmers and entrepreneurs.
{"title":"Impact of induced mutation-derived genetic variability, genotype and varieties for quantitative and qualitative traits in <i>Mentha</i> species.","authors":"Priyanka Prasad, Akancha Gupta, Vagmi Singh, Birendra Kumar","doi":"10.1080/09553002.2023.2263595","DOIUrl":"10.1080/09553002.2023.2263595","url":null,"abstract":"<p><strong>Purpose: </strong>The genus <i>Mentha</i> spp. is an aromatic herb from the family 'Lamiaceae'. It is extensively predominant in temperate and sub-temperate regions of the world. The essential oil of this species is enriched with broad aroma constituents extensively utilized in food, beverages, flavor, cosmetics, perfumery, and pharmaceutical enterprises. With the global menthol market size estimated to be worth USD 765 million in 2022, India (accompanied by China and Brazil) is the world's primary manufacturer, consumer, and exporter of <i>Mentha</i> oil. Despite prominent global demand, the crucial bottleneck in mint cultivation is the need for more superior commercial cultivars. Predominant vegetative propagation mode with difficulties in manual emasculation, differential blooming times, sterile/sub-sterile hybrids, and low seed viability are the primary containment in creating genetic variability by classical breeding approaches. Therefore, genetic complications encountered in conventional breeding have led the breeders to apply mutation breeding as an alternative crop improvement approach in <i>Mentha</i> spp. These attempts at mutation breeding have produced some distinctive mutants as genetic pools for plant breeding programs, and some novel mutant mint cultivars have been made available for commercial cultivation.</p><p><strong>Conclusions: </strong>The prime strategy in mutation-based breeding has proven an adept means of encouraging the expression of recessive genes and producing new genetic variations. The present review comprises a significant contribution of mutation breeding approaches in the development of mutant mint species and its effects on physiological variation, photosynthetic pigment, essential oil content and composition, phytochemical-mediated defense response, pathogen resistivity, and differential expression of genes related to terpenoid biogenesis. Development and diversification have led to the release of varieties, namely Todd's Mitcham, Murray Mitcham, Pranjal, Tushar, and Kukrail in <i>M. piperita</i> L., Mukta, and Pratik in <i>M. cardiaca</i> Baker, Neera in <i>M. spicata</i> L., Kiran in <i>M. citrata</i> Ehrh., and Rose mint in <i>M. arvensis</i> L. that have revolutionized and uplifted mint cultivation leading to economic gain by the farmers and entrepreneurs.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"151-160"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180025","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: 2024-01-09DOI: 10.1080/09553002.2023.2245463
Luana Hafner, Linda Walsh, Werner Rühm
Purpose: Risk analyses, based on relative biological effectiveness (RBE) estimates for neutrons relative to gammas, were performed; and the change in the curvature of the risk to dose response with increasing neutron RBE was analyzed using all solid cancer mortality data from the Radiation Effect Research Foundation (RERF). Results were compared to those based on incidence data.
Materials and methods: This analysis is based on RERF mortality data with separate neutron and gamma doses for colon doses, from which organ averaged doses could be calculated. A model for risk ratio variation with RBE was developed.
Results: The best estimate of the neutron RBE considering mortality data was 200 (95% confidence interval (CI): 50-1010) for colon dose using the weighted-dose approach and for organ averaged dose 110 (95% CI: 30-350). The ERR risk ratios for all solid cancers combined, for the best fitting neutron RBE estimate and the neutron RBE of 10 result in a ratio of 0.54 (95% CI: 0.17-0.85) for colon dose and 0.55 (95% CI: 0.18-0.87) for organ averaged dose. The risk to dose response curvature became significantly negative (concave down) with increasing RBE, at a neutron RBE of 170 using colon dose and at an RBE of 90 using organ averaged dose for males when fitting a linear-quadratic dose response. For females, the curvature decreased toward linearity with increasing neutron RBE and remained significantly positive until RBE of 80 and 40 using colon and organ averaged dose, respectively. For higher neutron RBEs, no significant conclusion could be drawn about the shape of the dose-response curve.
Conclusions: Application of neutron RBE values higher than 10 results in substantially reduced cancer mortality risk estimates and a significant reduction in curvature of the risk to dose responses for males. Using mortality data, the best fitting neutron RBE is much higher than when incidence data is used. The neutron RBE ranges covered by the overlap in the CIs from both the mortality and incidence analyses are 50-190 using colon dose and in all cases, the best fitting neutron RBE and lower 95% CI are higher than the value of 10 traditionally applied by the RERF. Therefore, it is recommended to consider uncertainties in neutron RBE values when calculating radiation risks and discussing the shape of dose responses using Japanese A-bomb survivors data.
{"title":"Assessing the impact of neutron relative biological effectiveness on all solid cancer mortality risks in the Japanese atomic bomb survivors.","authors":"Luana Hafner, Linda Walsh, Werner Rühm","doi":"10.1080/09553002.2023.2245463","DOIUrl":"10.1080/09553002.2023.2245463","url":null,"abstract":"<p><strong>Purpose: </strong>Risk analyses, based on relative biological effectiveness (RBE) estimates for neutrons relative to gammas, were performed; and the change in the curvature of the risk to dose response with increasing neutron RBE was analyzed using all solid cancer <i>mortality</i> data from the Radiation Effect Research Foundation (RERF). Results were compared to those based on incidence data.</p><p><strong>Materials and methods: </strong>This analysis is based on RERF mortality data with separate neutron and gamma doses for colon doses, from which organ averaged doses could be calculated. A model for risk ratio variation with RBE was developed.</p><p><strong>Results: </strong>The best estimate of the neutron RBE considering mortality data was 200 (95% confidence interval (CI): 50-1010) for colon dose using the weighted-dose approach and for organ averaged dose 110 (95% CI: 30-350). The ERR risk ratios for all solid cancers combined, for the best fitting neutron RBE estimate and the neutron RBE of 10 result in a ratio of 0.54 (95% CI: 0.17-0.85) for colon dose and 0.55 (95% CI: 0.18-0.87) for organ averaged dose. The risk to dose response curvature became significantly negative (concave down) with increasing RBE, at a neutron RBE of 170 using colon dose and at an RBE of 90 using organ averaged dose for males when fitting a linear-quadratic dose response. For females, the curvature decreased toward linearity with increasing neutron RBE and remained significantly positive until RBE of 80 and 40 using colon and organ averaged dose, respectively. For higher neutron RBEs, no significant conclusion could be drawn about the shape of the dose-response curve.</p><p><strong>Conclusions: </strong>Application of neutron RBE values higher than 10 results in substantially reduced cancer mortality risk estimates and a significant reduction in curvature of the risk to dose responses for males. Using mortality data, the best fitting neutron RBE is much higher than when incidence data is used. The neutron RBE ranges covered by the overlap in the CIs from both the mortality and incidence analyses are 50-190 using colon dose and in all cases, the best fitting neutron RBE and lower 95% CI are higher than the value of 10 traditionally applied by the RERF. Therefore, it is recommended to consider uncertainties in neutron RBE values when calculating radiation risks and discussing the shape of dose responses using Japanese A-bomb survivors data.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"61-71"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41161309","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: 2023-12-06DOI: 10.1080/09553002.2023.2290293
Lu Yanting, Wang Bingkui, Zhang Mengchao, Ye Jing, Ye Shenghai
Purpose: Radiation mutagenesis, which typically involves gamma rays, is important for generating new rice germplasm resources. Determining the appropriate radiation dose range is critical for the success of radiation mutagenesis. Clarifying the sensitivity and tolerance of genotypically diverse rice varieties to gamma irradiation as well as the radiation-induced changes to reactive oxygen species (ROS) generation and antioxidant enzyme activities is crucial for increasing the utility of radiation mutagenesis in rice breeding programs.
Materials and methods: The seeds of the following four rice varieties with different genotypes were used as test materials: indica Zhe 1613, glutinous indica Zhe 1708, japonica Zhejing 100, and glutinous japonica Zhenuo 65. Additionally,60Co was used as the source of gamma rays. The rice seeds were irradiated with 14 doses (0, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750 Gy). Non-irradiated seeds were used as the control. The seedling survival rate for each variety was recorded at 3, 7, 14, and 28 days after sowing. Moreover, the median lethal dose (LD50) and critical dose (LD40) were calculated according to the seedling survival rates at 28 days after sowing. The seedling superoxide anion (O2•-), hydrogen peroxide (H2O2), and malondialdehyde (MDA) contents and the superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) activities were analyzed at 7 days after sowing.
Results: As the radiation dose increased, the seedling survival rate decreased. The seedling survival rate also decreased significantly as the number of days after sowing increased. Among the rice genotypes, the rank-order of the radiation tolerance was as follows: indica Zhe 1613 > glutinous indica Zhe 1708 > japonica Zhejing 100 > glutinous japonica Zhenuo 65. The LD50 values were 426.7 Gy for Zhe 1613, 329.2 Gy for Zhe 1708, 318.3 Gy for Zhejing 100, and 316.6 Gy for Zhenuo 65. Increases in the radiation dose resulted in significant increases in the seedling O2•- and H2O2 contents, but only up to a certain point. Further increases in the radiation dose caused the seedling O2•- and H2O2 contents to decrease. The H2O2 content for each variety peaked when the radiation dose was very close to the LD50. We propose that the radiation dose associated with the highest H2O2 content (±50 Gy) should be used as the recommended dose for the gamma irradiation of rice. The radiation dose that resulted in peak seedling O2•- contents in the analyzed rice varieties was very close to the LD40. In all rice varieties, the MDA conten
{"title":"Sensitivity of genotypically diverse rice varieties to radiation and the related changes to antioxidant enzyme activities.","authors":"Lu Yanting, Wang Bingkui, Zhang Mengchao, Ye Jing, Ye Shenghai","doi":"10.1080/09553002.2023.2290293","DOIUrl":"10.1080/09553002.2023.2290293","url":null,"abstract":"<p><strong>Purpose: </strong>Radiation mutagenesis, which typically involves gamma rays, is important for generating new rice germplasm resources. Determining the appropriate radiation dose range is critical for the success of radiation mutagenesis. Clarifying the sensitivity and tolerance of genotypically diverse rice varieties to gamma irradiation as well as the radiation-induced changes to reactive oxygen species (ROS) generation and antioxidant enzyme activities is crucial for increasing the utility of radiation mutagenesis in rice breeding programs.</p><p><strong>Materials and methods: </strong>The seeds of the following four rice varieties with different genotypes were used as test materials: <i>indica</i> Zhe 1613, glutinous <i>indica</i> Zhe 1708, <i>japonica</i> Zhejing 100, and glutinous <i>japonica</i> Zhenuo 65. Additionally,<sup>60</sup>Co was used as the source of gamma rays. The rice seeds were irradiated with 14 doses (0, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750 Gy). Non-irradiated seeds were used as the control. The seedling survival rate for each variety was recorded at 3, 7, 14, and 28 days after sowing. Moreover, the median lethal dose (LD<sub>50</sub>) and critical dose (LD<sub>40</sub>) were calculated according to the seedling survival rates at 28 days after sowing. The seedling superoxide anion (O<sub>2</sub><sup>•-</sup>), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), and malondialdehyde (MDA) contents and the superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) activities were analyzed at 7 days after sowing.</p><p><strong>Results: </strong>As the radiation dose increased, the seedling survival rate decreased. The seedling survival rate also decreased significantly as the number of days after sowing increased. Among the rice genotypes, the rank-order of the radiation tolerance was as follows: <i>indica</i> Zhe 1613 > glutinous <i>indica</i> Zhe 1708 > <i>japonica</i> Zhejing 100 > glutinous <i>japonica</i> Zhenuo 65. The LD<sub>50</sub> values were 426.7 Gy for Zhe 1613, 329.2 Gy for Zhe 1708, 318.3 Gy for Zhejing 100, and 316.6 Gy for Zhenuo 65. Increases in the radiation dose resulted in significant increases in the seedling O<sub>2</sub><sup>•-</sup> and H<sub>2</sub>O<sub>2</sub> contents, but only up to a certain point. Further increases in the radiation dose caused the seedling O<sub>2</sub><sup>•-</sup> and H<sub>2</sub>O<sub>2</sub> contents to decrease. The H<sub>2</sub>O<sub>2</sub> content for each variety peaked when the radiation dose was very close to the LD<sub>50</sub>. We propose that the radiation dose associated with the highest H<sub>2</sub>O<sub>2</sub> content (±50 Gy) should be used as the recommended dose for the gamma irradiation of rice. The radiation dose that resulted in peak seedling O<sub>2</sub><sup>•-</sup> contents in the analyzed rice varieties was very close to the LD<sub>40</sub>. In all rice varieties, the MDA conten","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"453-465"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465214","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: 2023-11-16DOI: 10.1080/09553002.2023.2277365
Dimitri Besset, Brahim Selmaoui, Stéphane Delanaud, Lisa Bessarion, Karen Chardon, René de Seze, André Leke, Erwan Stéphan-Blanchard
Purpose: The study objective was to assess the influence of radiofrequency electromagnetic fields (RF-EMF) exposure on sleep patterns in preterm newborns. We hypothesized that an increase in RF-EMF exposure levels would alter infants' sleep structure parameters.
Materials and methods: Individual, continuous measurements of RF-EMF levels were performed in 29 hospitalized preterm newborns throughout the first 21 days after birth. The last day, overnight sleep structure was recorded by polysomnography. Relationships between both chronic (three-week period) and acute (polysomnographic period) RF-EMF levels with sleep parameters were computed.
Results: At median levels, the main chronic effect was an increase in indeterminate sleep with RF-EMF exposure. At the highest exposure levels found in our study, an increase in RF-EMF levels increased sleep fragmentation. No significant relationship was found between acute RF-EMF levels and sleep parameters.
Conclusions: Despite no consolidated disruption in sleep structure, this study is the first to show that some sleep parameters seem to have a certain sensitivity to chronic - but not acute - RF-EMF exposure in preterm newborns. Further studies are needed to confirm our results and examine possible mid- to long-term, sleep-related cardiorespiratory and neurodevelopmental outcomes.
{"title":"Influence of radiofrequency electromagnetic fields exposure on sleep patterns in preterm neonates.","authors":"Dimitri Besset, Brahim Selmaoui, Stéphane Delanaud, Lisa Bessarion, Karen Chardon, René de Seze, André Leke, Erwan Stéphan-Blanchard","doi":"10.1080/09553002.2023.2277365","DOIUrl":"10.1080/09553002.2023.2277365","url":null,"abstract":"<p><strong>Purpose: </strong>The study objective was to assess the influence of radiofrequency electromagnetic fields (RF-EMF) exposure on sleep patterns in preterm newborns. We hypothesized that an increase in RF-EMF exposure levels would alter infants' sleep structure parameters.</p><p><strong>Materials and methods: </strong>Individual, continuous measurements of RF-EMF levels were performed in 29 hospitalized preterm newborns throughout the first 21 days after birth. The last day, overnight sleep structure was recorded by polysomnography. Relationships between both chronic (three-week period) and acute (polysomnographic period) RF-EMF levels with sleep parameters were computed.</p><p><strong>Results: </strong>At median levels, the main chronic effect was an increase in indeterminate sleep with RF-EMF exposure. At the highest exposure levels found in our study, an increase in RF-EMF levels increased sleep fragmentation. No significant relationship was found between acute RF-EMF levels and sleep parameters.</p><p><strong>Conclusions: </strong>Despite no consolidated disruption in sleep structure, this study is the first to show that some sleep parameters seem to have a certain sensitivity to chronic - but not acute - RF-EMF exposure in preterm newborns. Further studies are needed to confirm our results and examine possible mid- to long-term, sleep-related cardiorespiratory and neurodevelopmental outcomes.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"427-432"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400831","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: 2024-03-05DOI: 10.1080/09553002.2024.2324472
Marco Durante
Purpose: Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberrations in blood cells irradiated ex-vivo. The explanation was based on the volume effect, i.e. the sparing of larger volumes of normal tissue in Bragg peak therapy. Here we will review the current knowledge about the difference in lymphopenia between particle and photon therapy and the consequences.
Conclusions: There is nowadays an overwhelming evidence that particle therapy reduces significantly the radiotherapy-induced lymphopenia in several tumor sites. Because lymphopenia turns down the immune response to checkpoint inhibitors, it can be predicted that particle therapy may be the ideal partner for combined radiation and immunotherapy treatment and should be selected for patients where severe lymphopenia is expected after X-rays.
目的:淋巴细胞减少症现在已被普遍认为是放疗的一个不利预后因素。早在本世纪初,我们就已经证明,与 X 射线相比,高能碳离子对放疗患者淋巴细胞的损伤更小,即使重离子在诱导体内照射血细胞染色体畸变方面单位剂量的效果更好。解释的依据是体积效应,即在布拉格峰治疗中,较大体积的正常组织不受影响。在此,我们将回顾目前关于粒子和光子疗法在淋巴细胞减少症方面的差异及其后果的知识:结论:如今有大量证据表明,粒子疗法可显著减少多个肿瘤部位放疗引起的淋巴细胞减少症。由于淋巴细胞减少会降低对检查点抑制剂的免疫反应,因此可以预测,粒子疗法可能是放疗与免疫疗法联合治疗的理想搭档,X射线后预计会出现严重淋巴细胞减少的患者应选择粒子疗法。
{"title":"Kaplan lecture 2023: lymphopenia in particle therapy.","authors":"Marco Durante","doi":"10.1080/09553002.2024.2324472","DOIUrl":"10.1080/09553002.2024.2324472","url":null,"abstract":"<p><strong>Purpose: </strong>Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberrations in blood cells irradiated ex-vivo. The explanation was based on the volume effect, i.e. the sparing of larger volumes of normal tissue in Bragg peak therapy. Here we will review the current knowledge about the difference in lymphopenia between particle and photon therapy and the consequences.</p><p><strong>Conclusions: </strong>There is nowadays an overwhelming evidence that particle therapy reduces significantly the radiotherapy-induced lymphopenia in several tumor sites. Because lymphopenia turns down the immune response to checkpoint inhibitors, it can be predicted that particle therapy may be the ideal partner for combined radiation and immunotherapy treatment and should be selected for patients where severe lymphopenia is expected after X-rays.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"669-677"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041204","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: We have previously demonstrated in a murine colorectal cancer model that normofractionated RT (normoRT: 18 × 2 Gy) induced MDSC infiltration and PD-L1 expression, while hypofractionated RT (hypoRT: 3 × 8 Gy) induced Treg. Here, we wanted to assess whether the association of normoRT with treatments that target two radiation-induced immunosuppressive pathways (MDSC and PD-L1) could improve tumor control.
Materials and methods: Subcutaneous tumors were induced using colon tumor cells (CT26) in immunocompetent mice (BALB/c) and were treated with RT alone (18 × 2 Gy or 3 × 8 Gy), or concomitantly with 5-Fluorouracil (5FU) (10 mg/kg) to deplete MDSC, and/or anti-PD-L1 (10 mg/kg). We assessed the impact of these combinations on tumor growth and immune cells infiltration by flow cytometry. In addition, we performed tumor rechallenge experiments and IFN-γ ELISpots to study the long-term memory response.
Results: Even though tumor growth was significantly delayed in the RT + 5FU compared to 5FU and untreated groups (p < .05), there was no significant difference between RT + 5FU (CRT) and RT alone. The rate of MDSC increased significantly 1 week after the end of normoRT (8.09% ± 1.03%, p < .05) and decreased with the addition of 5FU (3.39% ± 0.69%, p < .05). PD-L1 expressing tumor cells were increased after treatment. Adding anti-PD-L1 significantly delayed tumor growth, achieved the highest complete response rate, and induced a long-lasting protective specific anti-tumor immunity.
Conclusions: These results tend to demonstrate the interest of inhibiting two radiation-induced immunosuppressive mechanisms. In patients, the combination of normoRT with 5FU is already the standard of care in locally advanced rectal cancer. Adding an anti-PD-L1 to this treatment could show promising results.
{"title":"Targeting two radiation-induced immunosuppressive pathways to improve the efficacy of normofractionated radiation therapy in a preclinical colorectal cancer model.","authors":"Jihane Boustani, Benoit Lecoester, Jérémy Baude, Charlène Latour, Emeric Limagne, Riad Ladjohoulou, Véronique Morgand, Lisa Froidurot, François Ghiringhelli, Gilles Truc, Olivier Adotévi, Céline Mirjolet","doi":"10.1080/09553002.2024.2331115","DOIUrl":"10.1080/09553002.2024.2331115","url":null,"abstract":"<p><strong>Purpose: </strong>We have previously demonstrated in a murine colorectal cancer model that normofractionated RT (normoRT: 18 × 2 Gy) induced MDSC infiltration and PD-L1 expression, while hypofractionated RT (hypoRT: 3 × 8 Gy) induced Treg. Here, we wanted to assess whether the association of normoRT with treatments that target two radiation-induced immunosuppressive pathways (MDSC and PD-L1) could improve tumor control.</p><p><strong>Materials and methods: </strong>Subcutaneous tumors were induced using colon tumor cells (CT26) in immunocompetent mice (BALB/c) and were treated with RT alone (18 × 2 Gy or 3 × 8 Gy), or concomitantly with 5-Fluorouracil (5FU) (10 mg/kg) to deplete MDSC, and/or anti-PD-L1 (10 mg/kg). We assessed the impact of these combinations on tumor growth and immune cells infiltration by flow cytometry. In addition, we performed tumor rechallenge experiments and IFN-γ ELISpots to study the long-term memory response.</p><p><strong>Results: </strong>Even though tumor growth was significantly delayed in the RT + 5FU compared to 5FU and untreated groups (<i>p</i> < .05), there was no significant difference between RT + 5FU (CRT) and RT alone. The rate of MDSC increased significantly 1 week after the end of normoRT (8.09% ± 1.03%, <i>p</i> < .05) and decreased with the addition of 5FU (3.39% ± 0.69%, <i>p</i> < .05). PD-L1 expressing tumor cells were increased after treatment. Adding anti-PD-L1 significantly delayed tumor growth, achieved the highest complete response rate, and induced a long-lasting protective specific anti-tumor immunity.</p><p><strong>Conclusions: </strong>These results tend to demonstrate the interest of inhibiting two radiation-induced immunosuppressive mechanisms. In patients, the combination of normoRT with 5FU is already the standard of care in locally advanced rectal cancer. Adding an anti-PD-L1 to this treatment could show promising results.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"912-921"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178368","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: 2024-06-26DOI: 10.1080/09553002.2024.2369105
Valtteri Nieminen, Maria-Viola Martikainen, Saija Kalliomäki, Tuomas Virén, Jan Seppälä, Jukka Juutilainen, Jonne Naarala, Jukka Luukkonen
Purpose: Earlier evidence suggests that extremely low frequency magnetic fields (ELF MFs) can modify the effects of carcinogenic agents. However, the studies conducted so far with ionizing radiation as the co-exposure agent are sparse and have provided inconclusive results. We investigated whether 50 Hz MFs alone, or in combination with ionizing radiation alter cell biological variables relevant to cancer and the biological effects of ionizing radiation.
Materials and methods: Human SH-SY5Y neuroblastoma cells were sham exposed or exposed to 100 or 500 µT MF for 24 h either before or after ionizing radiation exposure (0, 0.4 or 2 Gy). After the exposures, cells were assayed for viability, clonogenicity, reactive oxygen species, caspase-3 activity, and cell cycle distribution. Cell cycle distribution was assayed with propidium iodide staining followed by flow cytometry analysis and ROS levels were assayed together with cell viability by double staining with DeepRed and Sytox Blue followed by flow cytometry analysis.
Results: Increased caspase-3 activity was observed in cells exposed to 500 µT MF before or after ionizing radiation. Furthermore, exposure to the 500 µT MF after the ionizing radiation decreased the percentage of cells in S-phase. No changes in the ROS levels, clonogenicity, or viability of the cells were observed in the MF exposed groups compared to the corresponding sham exposed groups, and no MF effects were observed in cells exposed at 100 µT.
Conclusions: Only the 500 µT magnetic flux density affected SH-SY5Y cells significantly. The effects were small but may nevertheless help to understand how MFs modify the effects of ionizing radiation. The increase in caspase-3 activity may not reflect effects on apoptosis, as no changes were observed in the subG1 phase of the cell cycle. In contrast to some earlier findings, 50 Hz MF exposure after ionizing radiation was not less effective than MF treatment given prior to ionizing radiation.
{"title":"50 Hz magnetic field influences caspase-3 activity and cell cycle distribution in ionizing radiation exposed SH-SY5Y neuroblastoma cells.","authors":"Valtteri Nieminen, Maria-Viola Martikainen, Saija Kalliomäki, Tuomas Virén, Jan Seppälä, Jukka Juutilainen, Jonne Naarala, Jukka Luukkonen","doi":"10.1080/09553002.2024.2369105","DOIUrl":"10.1080/09553002.2024.2369105","url":null,"abstract":"<p><strong>Purpose: </strong>Earlier evidence suggests that extremely low frequency magnetic fields (ELF MFs) can modify the effects of carcinogenic agents. However, the studies conducted so far with ionizing radiation as the co-exposure agent are sparse and have provided inconclusive results. We investigated whether 50 Hz MFs alone, or in combination with ionizing radiation alter cell biological variables relevant to cancer and the biological effects of ionizing radiation.</p><p><strong>Materials and methods: </strong>Human SH-SY5Y neuroblastoma cells were sham exposed or exposed to 100 or 500 µT MF for 24 h either before or after ionizing radiation exposure (0, 0.4 or 2 Gy). After the exposures, cells were assayed for viability, clonogenicity, reactive oxygen species, caspase-3 activity, and cell cycle distribution. Cell cycle distribution was assayed with propidium iodide staining followed by flow cytometry analysis and ROS levels were assayed together with cell viability by double staining with DeepRed and Sytox Blue followed by flow cytometry analysis.</p><p><strong>Results: </strong>Increased caspase-3 activity was observed in cells exposed to 500 µT MF before or after ionizing radiation. Furthermore, exposure to the 500 µT MF after the ionizing radiation decreased the percentage of cells in S-phase. No changes in the ROS levels, clonogenicity, or viability of the cells were observed in the MF exposed groups compared to the corresponding sham exposed groups, and no MF effects were observed in cells exposed at 100 µT.</p><p><strong>Conclusions: </strong>Only the 500 µT magnetic flux density affected SH-SY5Y cells significantly. The effects were small but may nevertheless help to understand how MFs modify the effects of ionizing radiation. The increase in caspase-3 activity may not reflect effects on apoptosis, as no changes were observed in the subG1 phase of the cell cycle. In contrast to some earlier findings, 50 Hz MF exposure after ionizing radiation was not less effective than MF treatment given prior to ionizing radiation.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1183-1192"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461419","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: 2024-02-06DOI: 10.1080/09553002.2024.2309917
A Amrenova, C Baudin, E Ostroumova, J Stephens, R Anderson, D Laurier
Purpose: The purpose of this paper was to conduct a review of the studies published between 2018 and 2022 to investigate radiation-related effects in the offspring of human individuals exposed to ionizing radiation.
Methods: The search identified 807 publications, from which 9 studies were selected for detailed analysis to examine for effects in children whose parents were exposed to various types and doses of radiation.
Results: The review does not yield substantial evidence supporting intergenerational effects of radiation exposure in humans. However, caution is required when interpreting the results due to limitations in the majority of the published articles.
Conclusion: This review, covering the period 2018-2022, serves as an extension of the previous systematic review conducted by Stephens et al. (2024), which encompassed the years 1988-2018. Together, these two papers offer a comprehensive overview of the available evidence regarding the intergenerational effects of parental pre-conceptional exposure to ionizing radiation. Overall, the findings do not provide strong evidence supporting a significant association between adverse (or other) outcomes in unexposed children and parental preconception radiation exposure.
{"title":"Intergenerational effects of ionizing radiation: review of recent studies from human data (2018-2021).","authors":"A Amrenova, C Baudin, E Ostroumova, J Stephens, R Anderson, D Laurier","doi":"10.1080/09553002.2024.2309917","DOIUrl":"10.1080/09553002.2024.2309917","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this paper was to conduct a review of the studies published between 2018 and 2022 to investigate radiation-related effects in the offspring of human individuals exposed to ionizing radiation.</p><p><strong>Methods: </strong>The search identified 807 publications, from which 9 studies were selected for detailed analysis to examine for effects in children whose parents were exposed to various types and doses of radiation.</p><p><strong>Results: </strong>The review does not yield substantial evidence supporting intergenerational effects of radiation exposure in humans. However, caution is required when interpreting the results due to limitations in the majority of the published articles.</p><p><strong>Conclusion: </strong>This review, covering the period 2018-2022, serves as an extension of the previous systematic review conducted by Stephens et al. (2024), which encompassed the years 1988-2018. Together, these two papers offer a comprehensive overview of the available evidence regarding the intergenerational effects of parental pre-conceptional exposure to ionizing radiation. Overall, the findings do not provide strong evidence supporting a significant association between adverse (or other) outcomes in unexposed children and parental preconception radiation exposure.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1253-1263"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693670","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: Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms.
Materials and methods: A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1β were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA.
Results: ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1β, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells.
Conclusions: ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.
{"title":"Exploring the protective effect and mechanism of icariside II on the bladder in a rat model of radiation cystitis based on transcriptome sequencing.","authors":"Jun-Tao Sun, Chen-Li Pan, Yin-Hui Mao, Zhuo Wang, Ji-Lei Sun, Xiang-Xiang Zhang, Yong Yang, Zhi-Tao Wei, Yong-De Xu","doi":"10.1080/09553002.2024.2386982","DOIUrl":"10.1080/09553002.2024.2386982","url":null,"abstract":"<p><strong>Purpose: </strong>Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms.</p><p><strong>Materials and methods: </strong>A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1β were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA.</p><p><strong>Results: </strong>ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1β, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells.</p><p><strong>Conclusions: </strong>ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1493-1504"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019995","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}