TY - JOUR A1 - Reimann, Hauke A1 - Stopper, Helga A1 - Polak, Thomas A1 - Lauer, Martin A1 - Herrmann, Martin J. A1 - Deckert, Jürgen A1 - Hintzsche, Henning T1 - Micronucleus frequency in buccal mucosa cells of patients with neurodegenerative diseases JF - Scientific Reports N2 - Neurodegenerative diseases show an increase in prevalence and incidence, with the most prominent example being Alzheimer's disease. DNA damage has been suggested to play a role in the pathogenesis, but the exact mechanisms remain elusive. We enrolled 425 participants with and without neurodegenerative diseases and analyzed DNA damage in the form of micronuclei in buccal mucosa samples. In addition, other parameters such as binucleated cells, karyolytic cells, and karyorrhectic cells were quantified. No relevant differences in DNA damage and cytotoxicity markers were observed in patients compared to healthy participants. Furthermore, other parameters such as lifestyle factors and diseases were also investigated. Overall, this study could not identify a direct link between changes in buccal cells and neurogenerative diseases, but highlights the influence of lifestyle factors and diseases on the human buccal cytome. KW - peripheral-blood lymphocytes KW - Alzheimers disease KW - DNA damage KW - cognitive impairment KW - cytome biomarkers KW - diagnosis KW - association KW - assay KW - life Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231430 VL - 10 ER - TY - JOUR A1 - Reimann, Hauke A1 - Stopper, Helga A1 - Hintzsche, Henning T1 - Long-term fate of etoposide-induced micronuclei and micronucleated cells in Hela-H2B-GFP cells JF - Archives of Toxicology N2 - Micronuclei are small nuclear cellular structures containing whole chromosomes or chromosomal fragments. While there is a lot of information available about the origin and formation of micronuclei, less is known about the fate of micronuclei and micronucleated cells. Possible fates include extrusion, degradation, reincorporation and persistence. Live cell imaging was performed to quantitatively analyse the fates of micronuclei and micronucleated cells occurring in vitro. Imaging was conducted for up to 96 h in HeLa-H2B-GFP cells treated with 0.5, 1 and 2 µg/ml etoposide. While a minority of micronuclei was reincorporated into the main nucleus during mitosis, the majority of micronuclei persisted without any alterations. Degradation and extrusion were observed rarely or never. The presence of micronuclei affected the proliferation of the daughter cells and also had an influence on cell death rates. Mitotic errors were found to be clearly increased in micronucleus-containing cells. The results show that micronuclei and micronucleated cells can, although delayed in cell cycle, sustain for multiple divisions. KW - micronuclei KW - cell fate KW - etoposide KW - live imaging KW - DNA damage Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235039 SN - 0340-5761 VL - 94 ER - TY - JOUR A1 - Winkelbeiner, Nicola A1 - Wandt, Viktoria K. A1 - Ebert, Franziska A1 - Lossow, Kristina A1 - Bankoglu, Ezgi E. A1 - Martin, Maximilian A1 - Mangerich, Aswin A1 - Stopper, Helga A1 - Bornhorst, Julia A1 - Kipp, Anna P. A1 - Schwerdtle, Tanja T1 - A multi-endpoint approach to base excision repair incision activity augmented by PARylation and DNA damage levels in mice: impact of sex and age JF - International Journal of Molecular Sciences N2 - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery. KW - maintenance of genomic integrity KW - ageing KW - sex KW - DNA damage KW - base excision repair (incision activity) KW - DNA damage response KW - poly(ADP-ribosyl)ation KW - liver Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285706 SN - 1422-0067 VL - 21 IS - 18 ER -