دورية أكاديمية
Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
| العنوان: | Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation |
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| المؤلفون: | Brackmann, Lara Kim, Poplawski, Alicia, Grandt, Caine Lucas, Schwarz, Heike, Hankeln, Thomas, Rapp, Steffen, Zahnreich, Sebastian, Galetzka, Danuta, Schmitt, Iris, Grad, Christian, Eckhard, Lukas, Mirsch, Johanna, Blettner, Maria, Scholz-Kreisel, Peter, Hess, Moritz, Binder, Harald, Schmidberger, Heinz, Marron, Manuela |
| المصدر: | Molecular medicine, 26:85 |
| سنة النشر: | 2020 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Gene-radiation interaction, RNA sequencing, Childhood cancer, High dose, Fibroblasts, Low dose, Second primary neoplasm, IPA, Ionizing radiation |
| الوصف: | BACKGROUND: Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. METHODS: Fibroblasts from skin biopsies of 15 cell donors were exposed to a high (2Gy) and a low (0.05Gy) dose of X-rays. RNA was extracted and sequenced 2 h and 4 h after exposure. Differentially expressed genes with an adjusted p-value < 0.05 were flagged and used for pathway analyses including prediction of upstream and downstream effects. Principal component analyses were used to examine the effect of two different sequencing runs on quality metrics and variation in expression and alignment and for explorative analysis of the radiation dose and time point of analysis. RESULTS: More genes were differentially expressed 4 h after exposure to low and high doses of radiation than after 2 h. In experiments with high dose irradiation and RNA sequencing after 4 h, inactivation of the FAT10 cancer signaling pathway and activation of gluconeogenesis I, glycolysis I, and prostanoid biosynthesis was observed taking p-value (< 0.05) and (in) activating z-score (≥2.00 or ≤ − 2.00) into account. Two hours after high dose irradiation, inactivation of small cell lung cancer signaling was observed. For low dose irradiation experiments, we did not detect any significant (p < 0.05 and z-score ≥ 2.00 or ≤ − 2.00) activated or inactivated pathways for both time points. CONCLUSIONS: Compared to 2 h after irradiation, a higher number of differentially expressed genes were found 4 h ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6425806Test; https://doi.org/10.1186/s10020-020-00203-0Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488023Test/; https://molmed.biomedcentral.com/articles/10.1186/s10020-020-00203-0#Sec15Test |
| DOI: | 10.1186/s10020-020-00203-0 |
| DOI: | 10.1186/s10020-020-00203-0#Sec15 |
| الإتاحة: | https://doi.org/10.1186/s10020-020-00203-0Test https://repository.publisso.de/resource/frl:6425806Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488023Test/ |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.11AFB23E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s10020-020-00203-0 |
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