TY  - JOUR
A1  - Maierhofer, Anna
A1  - Flunkert, Julia
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Schindler, Detlev
A1  - Nanda, Indrajit
A1  - Haaf, Thomas
T1  - Analysis of global DNA methylation changes in primary human fibroblasts in the early phase following X-ray irradiation
JF  - PLoS ONE
N2  - 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 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.
KW  - DNA methylation
KW  - fibroblasts
KW  - methylation
KW  - alu elements
KW  - DNA damage
KW  - epigenetics
KW  - cancer treatment
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170895
VL  - 12
IS  - 5
ER  - 
TY  - JOUR
A1  - Scherzad, Agmal
A1  - Meyer, Till
A1  - Kleinsasser, Norbert
A1  - Hackenberg, Stephan
T1  - Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity Short Running Title: Genotoxicity of ZnO NPs
JF  - Materials
N2  - Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.
KW  - zinc oxide nanoparticles
KW  - genotoxicity
KW  - DNA damage
KW  - ROS
KW  - autophagy
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169948
VL  - 10
IS  - 12
ER  -