@article{RuszkiewiczPapatheodorouJaecketal.2023,
  author    = {Ruszkiewicz, Joanna and Papatheodorou, Ylea and J{\"a}ck, Nathalie and Melzig, Jasmin and Eble, Franziska and Pirker, Annika and Thomann, Marius and Haberer, Andreas and Rothmiller, Simone and B{\"u}rkle, Alexander and Mangerich, Aswin},
  title     = {NAD+ Acts as a protective factor in cellular stress response to DNA alkylating agents},
  series = {Cells : open access journal},
  volume    = {12},
  journal   = {Cells : open access journal},
  number    = {19},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2073-4409},
  doi       = {10.3390/cells12192396},
  pages     = {22},
  year      = {2023},
  abstract  = {Sulfur mustard (SM) and its derivatives are potent genotoxic agents, which have been shown to trigger the activation of poly (ADP-ribose) polymerases (PARPs) and the depletion of their substrate, nicotinamide adenine dinucleotide (NAD+). NAD+ is an essential molecule involved in numerous cellular pathways, including genome integrity and DNA repair, and thus, NAD+ supplementation might be beneficial for mitigating mustard-induced (geno)toxicity. In this study, the role of NAD+ depletion and elevation in the genotoxic stress response to SM derivatives, i.e., the monofunctional agent 2-chloroethyl-ethyl sulfide (CEES) and the crosslinking agent mechlorethamine (HN2), was investigated with the use of NAD+ booster nicotinamide riboside (NR) and NAD+ synthesis inhibitor FK866. The effects were analyzed in immortalized human keratinocytes (HaCaT) or monocyte-like cell line THP-1. In HaCaT cells, NR supplementation, increased NAD+ levels, and elevated PAR response, however, did not affect ATP levels or DNA damage repair, nor did it attenuate long- and short-term cytotoxicities. On the other hand, the depletion of cellular NAD+ via FK866 sensitized HaCaT cells to genotoxic stress, particularly CEES exposure, whereas NR supplementation, by increasing cellular NAD+ levels, rescued the sensitizing FK866 effect. Intriguingly, in THP-1 cells, the NR-induced elevation of cellular NAD+ levels did attenuate toxicity of the mustard compounds, especially upon CEES exposure. Together, our results reveal that NAD+ is an important molecule in the pathomechanism of SM derivatives, exhibiting compound-specificity. Moreover, the cell line-dependent protective effects of NR are indicative of system-specificity of the application of this NAD+ booster.},
  language  = {en}
}
@article{WinkelbeinerWandtEbertetal.2020,
  author    = {Winkelbeiner, Nicola Lisa and Wandt, Viktoria Klara Veronika and Ebert, Franziska and Lossow, Kristina and Bankoglu, Ezgi E. and Martin, Maximilian and Mangerich, Aswin and Stopper, Helga and Bornhorst, Julia and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  publisher = {Molecular Diversity Preservation International},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21186600},
  pages     = {19},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{BasaranDuyduUstundagetal.2019,
  author    = {Basaran, Nursen and Duydu, Yalcin and Ustundag, Aylin and Taner, Gokce and Aydin, Sevtap and Anlar, Hatice Gul and Yalcin, Can {\"O}zg{\"u}r and Bacanli, Merve and Aydos, Kaan and Atabekoglu, Cem Somer and Golka, Klaus and Ickstadt, Katja and Schwerdtle, Tanja and Werner, Matthias and Meyer, S{\"o}ren and Bolt, Hermann M.},
  title     = {Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions},
  series = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis},
  volume    = {843},
  journal   = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1383-5718},
  doi       = {10.1016/j.mrgentox.2018.12.013},
  pages     = {33 -- 39},
  year      = {2019},
  abstract  = {Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.},
  language  = {en}
}
@article{BaşaranDuyduUestuendağetal.2019,
  author    = {Ba{\c{s}}aran, Nur{\c{s}}en and Duydu, Yal{\c{c}}{\i}n and {\"U}st{\"u}ndağ, Aylin and Taner, G{\"o}k{\c{c}}e and Aydin Dilsiz, Sevtap and Anlar, Hatice G{\"u}l and Yal{\c{c}}in, Can {\"O}zg{\"u}r and Bacanli, Merve and Golka, Klaus and Schwerdtle, Tanja and Bolt, Hermann M.},
  title     = {Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females DNA damage in lymphocytes and buccal cells of boron exposed females},
  series = {Journal of trace elements in medicine and biology},
  volume    = {53},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier B.V.},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2019.03.004},
  pages     = {150 -- 153},
  year      = {2019},
  abstract  = {Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boronpoor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.},
  language  = {en}
}
@article{RackwitzBald2018,
  author    = {Rackwitz, Jenny and Bald, Ilko},
  title     = {Low-energy electron-induced strand breaks in telomere-derived DNA sequences},
  series = {Chemistry - a European journal},
  volume    = {24},
  journal   = {Chemistry - a European journal},
  number    = {18},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {0947-6539},
  doi       = {10.1002/chem.201705889},
  pages     = {4680 -- 4688},
  year      = {2018},
  abstract  = {During cancer radiation therapy high-energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low-energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low-energy electron-induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G-rich sequences. Here, we use DNA origami platforms to expose G-rich telomere sequences to low-energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5′-(TTA GGG)2 is more sensitive to low-energy electrons than an intermixed sequence 5′-(TGT GTG A)2 confirming the unique electronic properties resulting from G-stacking. With increasing length of the oligonucleotide (i.e., going from 5′-(GGG ATT)2 to 5′-(GGG ATT)4), both the variety of topology and the electron-induced strand break cross sections increase. Addition of K+ ions decreases the strand break cross section for all sequences that are able to fold G-quadruplexes or G-intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low-energy electron-induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy.},
  language  = {en}
}