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Analysis of global DNA methylation changes in primary human fibroblasts in the early phase following X-ray irradiation

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170895
  • Epigenetic alterations may contribute to the generation of cancer cells in a multi-step process of tumorigenesis following irradiation of normal body cells. Primary human fibroblasts with intact cell cycle checkpoints were used as a model to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic effects (within the first cell cycle) in the exposed cells. ELISA-based fluorometric assays were consistent with slightly reduced global DNA methylation and hydroxymethylation, however the observed between-group differences wereEpigenetic alterations may contribute to the generation of cancer cells in a multi-step process of tumorigenesis following irradiation of normal body cells. Primary human fibroblasts with intact cell cycle checkpoints were used as a model to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic effects (within the first cell cycle) in the exposed cells. ELISA-based fluorometric assays were consistent with slightly reduced global DNA methylation and hydroxymethylation, however the observed between-group differences were usually not significant. Similarly, bisulfite pyrosequencing of interspersed LINE-1 repeats and centromeric α-satellite DNA did not detect significant methylation differences between irradiated and non-irradiated cultures. Methylation of interspersed ALU repeats appeared to be slightly increased (one percentage point; p = 0.01) at 6 h after irradiation with 4 Gy. Single-cell analysis showed comparable variations in repeat methylation among individual cells in both irradiated and control cultures. Radiation-induced changes in global repeat methylation, if any, were much smaller than methylation variation between different fibroblast strains. Interestingly, α-satellite DNA methylation positively correlated with gestational age. Finally, 450K methylation arrays mainly targeting genes and CpG islands were used for global DNA methylation analysis. There were no detectable methylation differences in genic (promoter, 5' UTR, first exon, gene body, 3' UTR) and intergenic regions between irradiated and control fibroblast cultures. Although we cannot exclude minor effects, i.e. on individual CpG sites, collectively our data suggest that global DNA methylation remains rather stable in irradiated normal body cells in the early phase of DNA damage response.show moreshow less

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Metadaten
Author: Anna Maierhofer, Julia Flunkert, Marcus Dittrich, Tobias Müller, Detlev Schindler, Indrajit Nanda, Thomas Haaf
URN:urn:nbn:de:bvb:20-opus-170895
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Humangenetik
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2017
Volume:12
Issue:5
Pagenumber:e0177442
Source:PLoS ONE 12(5):e0177442 (2017). DOI: 10.1371/journal.pone.0177442
DOI:https://doi.org/10.1371/journal.pone.0177442
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28489894
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 611 Menschliche Anatomie, Zytologie, Histologie
Tag:DNA damage; DNA methylation; alu elements; cancer treatment; epigenetics; fibroblasts; methylation
Release Date:2019/10/14
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International