Cargando…
Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs
The biological effects of low-dose-rate (LDR) radiation exposure in nuclear power plant accidents and medical uses of ionizing radiation (IR), although being a social concern, remain unclear. In this study, we evaluated the effects of LDR-IR on global gene expression in human cells and aimed to clar...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833988/ https://www.ncbi.nlm.nih.gov/pubmed/35159310 http://dx.doi.org/10.3390/cells11030501 |
_version_ | 1784649071176187904 |
---|---|
author | Shimabukuro, Kiichi Fukazawa, Takahiro Kanai, Akinori Kawai, Hidehiko Mekata, Kengo Hirohashi, Nobuyuki Kakimoto, Naoya Tanimoto, Keiji |
author_facet | Shimabukuro, Kiichi Fukazawa, Takahiro Kanai, Akinori Kawai, Hidehiko Mekata, Kengo Hirohashi, Nobuyuki Kakimoto, Naoya Tanimoto, Keiji |
author_sort | Shimabukuro, Kiichi |
collection | PubMed |
description | The biological effects of low-dose-rate (LDR) radiation exposure in nuclear power plant accidents and medical uses of ionizing radiation (IR), although being a social concern, remain unclear. In this study, we evaluated the effects of LDR-IR on global gene expression in human cells and aimed to clarify the mechanisms. RNA-seq analyses demonstrated that relatively low dose rates of IR modify gene expression levels in TIG-3 cells under normoxic conditions, but those effects were attenuated under hypoxia-mimicking conditions. Gene set enrichment analysis demonstrated that LDR-IR significantly decreased gene expression related to cell division, cell cycle, mitosis, and the Aurora kinase B and FOXM1 pathways. Quantitative RT-PCR confirmed the down-regulation of AURKB and FOXM1 genes in TIG-3 cells with LDR-IR or hypoxia-mimicking treatments without any dose-rate effect. Knock-down experiments suggested that HIF-1α and HIF-2α, as well as DEC1, participated in down-regulation of AURKB and FOXM1 under DFOM treatments, but to a lesser extent under LDR-IR treatment. FACS and microscopic analyses demonstrated that LDR-IR induced G0/G1 arrest and increased micronucleus or chromosome condensation. Finally, MTT assays demonstrated that LDR-IR decreased sensitivity to paclitaxel or barasertib in TIG-3 cells but not in A549 cells. In conclusion, LDR-IR modifies global gene expression and cell cycle control, resulting in a reduction of sensitivity to anti-cancer chemotherapy in non-cancer cells and thus a reduction in untoward effects (GA). |
format | Online Article Text |
id | pubmed-8833988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88339882022-02-12 Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs Shimabukuro, Kiichi Fukazawa, Takahiro Kanai, Akinori Kawai, Hidehiko Mekata, Kengo Hirohashi, Nobuyuki Kakimoto, Naoya Tanimoto, Keiji Cells Article The biological effects of low-dose-rate (LDR) radiation exposure in nuclear power plant accidents and medical uses of ionizing radiation (IR), although being a social concern, remain unclear. In this study, we evaluated the effects of LDR-IR on global gene expression in human cells and aimed to clarify the mechanisms. RNA-seq analyses demonstrated that relatively low dose rates of IR modify gene expression levels in TIG-3 cells under normoxic conditions, but those effects were attenuated under hypoxia-mimicking conditions. Gene set enrichment analysis demonstrated that LDR-IR significantly decreased gene expression related to cell division, cell cycle, mitosis, and the Aurora kinase B and FOXM1 pathways. Quantitative RT-PCR confirmed the down-regulation of AURKB and FOXM1 genes in TIG-3 cells with LDR-IR or hypoxia-mimicking treatments without any dose-rate effect. Knock-down experiments suggested that HIF-1α and HIF-2α, as well as DEC1, participated in down-regulation of AURKB and FOXM1 under DFOM treatments, but to a lesser extent under LDR-IR treatment. FACS and microscopic analyses demonstrated that LDR-IR induced G0/G1 arrest and increased micronucleus or chromosome condensation. Finally, MTT assays demonstrated that LDR-IR decreased sensitivity to paclitaxel or barasertib in TIG-3 cells but not in A549 cells. In conclusion, LDR-IR modifies global gene expression and cell cycle control, resulting in a reduction of sensitivity to anti-cancer chemotherapy in non-cancer cells and thus a reduction in untoward effects (GA). MDPI 2022-01-31 /pmc/articles/PMC8833988/ /pubmed/35159310 http://dx.doi.org/10.3390/cells11030501 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shimabukuro, Kiichi Fukazawa, Takahiro Kanai, Akinori Kawai, Hidehiko Mekata, Kengo Hirohashi, Nobuyuki Kakimoto, Naoya Tanimoto, Keiji Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs |
title | Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs |
title_full | Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs |
title_fullStr | Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs |
title_full_unstemmed | Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs |
title_short | Low-Dose-Rate Irradiation Suppresses the Expression of Cell Cycle-Related Genes, Resulting in Modification of Sensitivity to Anti-Cancer Drugs |
title_sort | low-dose-rate irradiation suppresses the expression of cell cycle-related genes, resulting in modification of sensitivity to anti-cancer drugs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833988/ https://www.ncbi.nlm.nih.gov/pubmed/35159310 http://dx.doi.org/10.3390/cells11030501 |
work_keys_str_mv | AT shimabukurokiichi lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT fukazawatakahiro lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT kanaiakinori lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT kawaihidehiko lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT mekatakengo lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT hirohashinobuyuki lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT kakimotonaoya lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs AT tanimotokeiji lowdoserateirradiationsuppressestheexpressionofcellcyclerelatedgenesresultinginmodificationofsensitivitytoanticancerdrugs |