Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts
IntroductionExperimental studies complement epidemiological data on the biological effects of low doses and dose rates of ionizing radiation and help in determining the dose and dose rate effectiveness factor.MethodsHuman VH10 skin fibroblasts exposed to 25, 50, and 100 mGy of 137Cs gamma radiation...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Public Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1297942/full |
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| author | Pamela Akuwudike Milagrosa López-Riego Michal Marczyk Michal Marczyk Zuzana Kocibalova Fabian Brückner Joanna Polańska Andrzej Wojcik Andrzej Wojcik Lovisa Lundholm |
| author_facet | Pamela Akuwudike Milagrosa López-Riego Michal Marczyk Michal Marczyk Zuzana Kocibalova Fabian Brückner Joanna Polańska Andrzej Wojcik Andrzej Wojcik Lovisa Lundholm |
| author_sort | Pamela Akuwudike |
| collection | DOAJ |
| description | IntroductionExperimental studies complement epidemiological data on the biological effects of low doses and dose rates of ionizing radiation and help in determining the dose and dose rate effectiveness factor.MethodsHuman VH10 skin fibroblasts exposed to 25, 50, and 100 mGy of 137Cs gamma radiation at 1.6, 8, 12 mGy/h, and at a high dose rate of 23.4 Gy/h, were analyzed for radiation-induced short- and long-term effects. Two sample cohorts, i.e., discovery (n = 30) and validation (n = 12), were subjected to RNA sequencing. The pool of the results from those six experiments with shared conditions (1.6 mGy/h; 24 h), together with an earlier time point (0 h), constituted a third cohort (n = 12).ResultsThe 100 mGy-exposed cells at all abovementioned dose rates, harvested at 0/24 h and 21 days after exposure, showed no strong gene expression changes. DMXL2, involved in the regulation of the NOTCH signaling pathway, presented a consistent upregulation among both the discovery and validation cohorts, and was validated by qPCR. Gene set enrichment analysis revealed that the NOTCH pathway was upregulated in the pooled cohort (p = 0.76, normalized enrichment score (NES) = 0.86). Apart from upregulated apical junction and downregulated DNA repair, few pathways were consistently changed across exposed cohorts. Concurringly, cell viability assays, performed 1, 3, and 6 days post irradiation, and colony forming assay, seeded just after exposure, did not reveal any statistically significant early effects on cell growth or survival patterns. Tendencies of increased viability (day 6) and reduced colony size (day 21) were observed at 12 mGy/h and 23.4 Gy/min. Furthermore, no long-term changes were observed in cell growth curves generated up to 70 days after exposure.DiscussionIn conclusion, low doses of gamma radiation given at low dose rates had no strong cytotoxic effects on radioresistant VH10 cells. |
| first_indexed | 2024-03-08T23:07:21Z |
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| institution | Directory Open Access Journal |
| issn | 2296-2565 |
| language | English |
| last_indexed | 2024-04-24T11:31:56Z |
| publishDate | 2023-12-01 |
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| spelling | doaj.art-5c86d6fb083a4b67b44523363d10d4642024-04-10T09:24:47ZengFrontiers Media S.A.Frontiers in Public Health2296-25652023-12-011110.3389/fpubh.2023.12979421297942Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblastsPamela Akuwudike0Milagrosa López-Riego1Michal Marczyk2Michal Marczyk3Zuzana Kocibalova4Fabian Brückner5Joanna Polańska6Andrzej Wojcik7Andrzej Wojcik8Lovisa Lundholm9Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Data Science and Engineering, Silesian University of Technology, Gliwice, PolandYale Cancer Center, Yale School of Medicine, New Haven, CT, United StatesCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Data Science and Engineering, Silesian University of Technology, Gliwice, PolandCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenInstitute of Biology, Jan Kochanowski University, Kielce, PolandCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenIntroductionExperimental studies complement epidemiological data on the biological effects of low doses and dose rates of ionizing radiation and help in determining the dose and dose rate effectiveness factor.MethodsHuman VH10 skin fibroblasts exposed to 25, 50, and 100 mGy of 137Cs gamma radiation at 1.6, 8, 12 mGy/h, and at a high dose rate of 23.4 Gy/h, were analyzed for radiation-induced short- and long-term effects. Two sample cohorts, i.e., discovery (n = 30) and validation (n = 12), were subjected to RNA sequencing. The pool of the results from those six experiments with shared conditions (1.6 mGy/h; 24 h), together with an earlier time point (0 h), constituted a third cohort (n = 12).ResultsThe 100 mGy-exposed cells at all abovementioned dose rates, harvested at 0/24 h and 21 days after exposure, showed no strong gene expression changes. DMXL2, involved in the regulation of the NOTCH signaling pathway, presented a consistent upregulation among both the discovery and validation cohorts, and was validated by qPCR. Gene set enrichment analysis revealed that the NOTCH pathway was upregulated in the pooled cohort (p = 0.76, normalized enrichment score (NES) = 0.86). Apart from upregulated apical junction and downregulated DNA repair, few pathways were consistently changed across exposed cohorts. Concurringly, cell viability assays, performed 1, 3, and 6 days post irradiation, and colony forming assay, seeded just after exposure, did not reveal any statistically significant early effects on cell growth or survival patterns. Tendencies of increased viability (day 6) and reduced colony size (day 21) were observed at 12 mGy/h and 23.4 Gy/min. Furthermore, no long-term changes were observed in cell growth curves generated up to 70 days after exposure.DiscussionIn conclusion, low doses of gamma radiation given at low dose rates had no strong cytotoxic effects on radioresistant VH10 cells.https://www.frontiersin.org/articles/10.3389/fpubh.2023.1297942/fulllow doselow dose ratedose and dose rate effectiveness factorradiation carcinogenesisfibroblasts |
| spellingShingle | Pamela Akuwudike Milagrosa López-Riego Michal Marczyk Michal Marczyk Zuzana Kocibalova Fabian Brückner Joanna Polańska Andrzej Wojcik Andrzej Wojcik Lovisa Lundholm Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts Frontiers in Public Health low dose low dose rate dose and dose rate effectiveness factor radiation carcinogenesis fibroblasts |
| title | Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts |
| title_full | Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts |
| title_fullStr | Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts |
| title_full_unstemmed | Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts |
| title_short | Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts |
| title_sort | short and long term effects of radiation exposure at low dose and low dose rate in normal human vh10 fibroblasts |
| topic | low dose low dose rate dose and dose rate effectiveness factor radiation carcinogenesis fibroblasts |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1297942/full |
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