TY - GEN A1 - Carlsson, Max J. A1 - Herzog, Natalie A1 - Felske, Christina A1 - Ackermann, Gabriel A1 - Regier, Alexander A1 - Wittmann, Simon A1 - Fernández Cereijo, Raúl A1 - Sturla, Shana J. A1 - Küpper, Jan-Heiner A1 - Fahrer, Jörg T1 - The DNA repair protein MGMT protects against the genotoxicity of N-nitrosodimethylamine, but Not N-nitrosodiethanolamine and N-nitrosomethylaniline, in human HepG2 liver cells with CYP2E1 expression T2 - Chemical research in toxicology N2 - N-nitrosamines are genotoxic contaminants that occur in the diet, consumer products, and the environment. More recently, N-nitrosamines were also detected as drug impurities. After uptake, N-nitrosamines undergo metabolic activation by cytochrome P450 monooxygenases (CYPs), resulting in DNA damage and tumor formation. In this study, the genotoxicity and cytotoxicity of three N-nitrosamines with structurally distinct substituents, N-nitrosodimethylamine (NDMA), N-nitrosodiethanolamine (NDELA) and N-nitrosomethylaniline (NMA), were analyzed in human HepG2 liver cell models proficient or deficient in CYP2E1 biotransformation. Furthermore, the impact of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) was investigated. The novel genetically engineered HepG2-CYP2E1 cell line strongly expressed CYP2E1, which was not detectable in wildtype (WT) HepG2 cells. We then confirmed that the CYP2E1 substrate NDMA caused O6-methyldesoxyguanosine adducts and DNA strand breaks in a CYP2E1-dependent manner, leading to cytotoxicity. By the same approach, we demonstrated that NDELA induced DNA strand breaks in HepG2-CYP2E1 cells, whereas no effect was observed for NMA. However, NMA was revealed to cause DNA cross-links. Furthermore, both NDELA and NMA were cytotoxic in HepG2-CYP2E1 cells, but not in WT cells. Subsequently, the pharmacological MGMT inhibitor O6-benzylguanine was used to deplete MGMT in both HepG2 cell models. MGMT inhibition clearly increased DNA strand break levels due to NDMA exposure, whereas DNA strand break formation by NDELA and NMA were not affected by inhibiting MGMT. In line with these findings, the clastogenic effects of NDMA were potentiated in the absence of MGMT. In contrast to that, NDELA- and NMA-induced clastogenicity was not influenced by MGMT inhibition. Taken together, our study revealed that all three structurally diverse N-nitrosamines are cytotoxic and clastogenic in a CYP2E1-dependent manner, while only NDMA and NDELA caused DNA strand breaks. Furthermore, we demonstrated for the first time that DNA repair by MGMT does not confer protection against NDELA and NMA-triggered DNA strand break induction and clastogenicity. KW - Adducts KW - Assays KW - Genetics KW - Toxicity KW - Transition metals Y1 - 2025 U6 - https://doi.org/10.1021/acs.chemrestox.5c00133 SN - 0893-228X VL - 38 IS - 6 SP - 1134 EP - 1146 PB - American Chemical Society (ACS) CY - New York, NY ER - TY - GEN A1 - Martienssen, Marion A1 - Simon, J. A1 - Schulze, R. T1 - Untersuchungen zum Einsatz von aufbereiteter Kfz-Kühlerflüssigkeit als organische C-Quelle bei der biologischen Sickerwasserbehandlung T2 - Korrespondenz Abwasser Y1 - 1997 SN - 0341-1540 VL - 44 IS - 9 SP - 1622 EP - 1627 ER - TY - GEN A1 - Martienssen, Marion A1 - Simon, J. T1 - Reinigung von Abwasser aus Emulsionsspaltanlagen durch kombinierten Einsatz von biologischer Behandlung und chemischer Naßoxidation T2 - Korespondenz Abwasser Y1 - 1997 SN - 0341-1540 VL - 44 IS - 1 SP - 110 EP - 114 ER - TY - CHAP A1 - Martienssen, Marion A1 - Schulze, R. A1 - Heinke, M. A1 - Pohl, W. A1 - Simon, J. T1 - Leistungen und Leistungsgrenzen unterschiedlicher biotechnologischer Verfahren für die Behandlung von Deponiesickerwasser T2 - 11. Jahrestagung der Biotechnologen, Nürnberg, 24. bis 26. Mai 1993, Kurzfassungen Y1 - 1993 SP - 43 EP - 44 PB - DECHEMA CY - Frankfurt am Main ER - TY - GEN A1 - Martienssen, Marion A1 - Schulze, R. A1 - Simon, J. T1 - Capacities and limits of three different technologies for the biological treatment of leachate from solid waste landfill sites Y1 - 1995 ER - TY - GEN A1 - Martienssen, Marion A1 - Simon, J. T1 - Effect of activated carbon on the biological treatment of oil-water emulsions Y1 - 1996 ER - TY - GEN A1 - Müller, Felix A1 - Torger, Bernhard A1 - Allertz, Peter J. A1 - Jähnichen, Klaus A1 - Keßler, Stefan A1 - Müller, Martin A1 - Simon, Frank A1 - Salchert, Katrin A1 - Mäurer, Haike A1 - Pospiech, Doris T1 - Multifunctional crosslinkable itaconic acid copolymers for enzyme immobilization T2 - European Polymer Journal N2 - UV-Crosslinkable itaconic copolymers are developed to provide new multifunctional materials for coatings which combine crosslinkable functionalities and the possibility to immobilize enzymes. The polymer-immobilized enzymes were used for water treatment to decompose persistent organic molecules. Introduction of suitable comonomers allows tailoring the mechanical and chemical properties for special applications. Copolymers containing MMA and itaconic anhydride were chosen because of the formation of long-term stable anhydride functionalities. These anhydride functionalities are employed to attach enzymes covalently. 4-Benzoylphenyl methacrylate is used as comonomer for UV-initiated crosslinking. Terpolymers are successfully obtained by radical copolymerization in solution. The copolymers are compared to poly(ethylene-alt-maleic anhydride) [P(EMA)] often used with respect to enzyme immobilization, activity and hydrolytic stability. The hydrolysis stability of the copolymers against water is studied by ATR-FTIR spectroscopy. Thin films are prepared on glass substrates in a layer-by-layer procedure by spin-coating. The layer formation is monitored by ATR-FTIR spectroscopy. UV-crosslinking of the copolymer films is performed taking the optimal irradiation dose that avoids polymer degradation. ATR-FTIR spectroscopy verifies the coupling reaction between amino groups of the enzyme and the anhydride groups on the surface of the crosslinked polymer film. The syringaldazine (4-hydroxy-3,5-dimethoxybenzaldehyde azine) test and 2,2´-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay demonstrate that the immobilized enzymes maintain their activities. The functional copolymers showed a significant effect in reduction of persistent organic pollutants in contaminated waste water. KW - ATR-FTIR spectroscopy KW - Crosslinking KW - Enzyme-immobilization KW - Itaconc acid KW - Methacrylate copolymer Y1 - 2018 U6 - https://doi.org/10.1016/j.eurpolymj.2018.03.014 VL - 102 SP - 47 EP - 55 ER - TY - GEN A1 - Krisponeit, Jon-Olaf A1 - Fischer, Simon A1 - Esser, Sven A1 - Moshnyaga, Vasily A1 - Schmidt, Thomas A1 - Piper, Louis F. J. A1 - Flege, Jan Ingo A1 - Falta, Jens T1 - The morphology of VO2/TiO2(001): terraces, facets, and cracks T2 - Scientific Reports N2 - Vanadium dioxide (VO2) features a pronounced, thermally-driven metal-to-insulator transition at 340 K. Employing epitaxial stress on rutile TiO2(001) substrates, the transition can be tuned to occur close to room temperature. Striving for applications in oxide-electronic devices, the lateral homogeneity of such samples must be considered as an important prerequisite for efforts towards miniaturization. Moreover, the preparation of smooth surfaces is crucial for vertically stacked devices and, hence, the design of functional interfaces. Here, the surface morphology of VO2/TiO2(001) films was analyzed by low-energy electron microscopy and diffraction as well as scanning probe microscopy. The formation of large terraces could be achieved under temperature-induced annealing, but also the occurrence of facets was observed and characterized. Further, we report on quasi-periodic arrangements of crack defects which evolve due to thermal stress under cooling. While these might impair some applicational endeavours, they may also present crystallographically well-oriented nano-templates of bulk-like properties for advanced approaches. KW - Vanadium dioxide (VO2) KW - rutile TiO2(001) KW - metal-to-insulator transition KW - morphology KW - crystallography KW - low-energy electron microscopy (LEEM) KW - low-energy electron diffraction (LEED) KW - scanning probe microscopy Y1 - 2020 U6 - https://doi.org/10.1038/s41598-020-78584-9 SN - 2045-2322 VL - 10 ER - TY - GEN A1 - Lyu, Yu-Xuan A1 - Fu, Qiang A1 - Wilczok, Dominika A1 - Ying, Kejun A1 - King, Aaron A1 - Antebi, Adam A1 - Vojta, Aleksandar A1 - Stolzing, Alexandra A1 - Moskalev, Alexey A1 - Georgievskaya, Anastasia A1 - Maier, Andrea B. A1 - Olsen, Andrea A1 - Groth, Anja A1 - Simon, Anna Katharina A1 - Brunet, Anne A1 - Jamil, Aisyah A1 - Kulaga, Anton A1 - Bhatti, Asif A1 - Yaden, Benjamin A1 - Pedersen, Bente Klarlund A1 - Schumacher, Björn A1 - Djordjevic, Boris A1 - Kennedy, Brian A1 - Chen, Chieh A1 - Huang, Christine Yuan A1 - Correll, Christoph U. A1 - Murphy, Coleen T. A1 - Ewald, Collin Y. A1 - Chen, Danica A1 - Valenzano, Dario Riccardo A1 - Sołdacki, Dariusz A1 - Erritzoe, David A1 - Meyer, David A1 - Sinclair, David A. A1 - Chini, Eduardo Nunes A1 - Teeling, Emma C. A1 - Morgen, Eric A1 - Verdin, Eric A1 - Vernet, Erik A1 - Pinilla, Estefano A1 - Fang, Evandro F. A1 - Bischof, Evelyne A1 - Mercken, Evi M. A1 - Finger, Fabian A1 - Kuipers, Folkert A1 - Pun, Frank W. A1 - Gyülveszi, Gabor A1 - Civiletto, Gabriele A1 - Zmudze, Garri A1 - Blander, Gil A1 - Pincus, Harold A. A1 - McClure, Joshua A1 - Kirkland, James L. A1 - Peyer, James A1 - Justice, Jamie N. A1 - Vijg, Jan A1 - Gruhn, Jennifer R. A1 - McLaughlin, Jerry A1 - Mannick, Joan A1 - Passos, João A1 - Baur, Joseph A. A1 - Betts-LaCroix, Joe A1 - Sedivy, John M. A1 - Speakman, John R. A1 - Shlain, Jordan A1 - Maltzahn, Julia von A1 - Andreasson, Katrin I. A1 - Moody, Kelsey A1 - Palikaras, Konstantinos A1 - Fortney, Kristen A1 - Niedernhofer, Laura J. A1 - Rasmussen, Lene Juel A1 - Veenhoff, Liesbeth M. A1 - Melton, Lisa A1 - Ferrucci, Luigi A1 - Quarta, Marco A1 - Koval, Maria A1 - Marinova, Maria A1 - Hamalainen, Mark A1 - Unfried, Maximilian A1 - Ringel, Michael S. A1 - Filipovic, Milos A1 - Topors, Mourad A1 - Mitin, Natalia A1 - Roy, Nawal A1 - Pintar, Nika A1 - Barzilai, Nir A1 - Binetti, Paolo A1 - Singh, Parminder A1 - Kohlhaas, Paul A1 - Robbins, Paul D. A1 - Rubin, Paul A1 - Fedichev, Peter O. A1 - Kamya, Petrina A1 - Muñoz-Canoves, Pura A1 - de Cabo, Rafael A1 - Faragher, Richard G. A. A1 - Konrad, Rob A1 - Ripa, Roberto A1 - Mansukhani, Robin A1 - Büttner, Sabrina A1 - Wickström, Sara A. A1 - Brunemeier, Sebastian A1 - Jakimov, Sergey A1 - Luo, Shan A1 - Rosenzweig-Lipson, Sharon A1 - Tsai, Shih-Yin A1 - Dimmeler, Stefanie A1 - Rando, Thomas A. A1 - Peterson, Tim R. A1 - Woods, Tina A1 - Wyss-Coray, Tony A1 - Finkel, Toren A1 - Strauss, Tzipora A1 - Gladyshev, Vadim N. A1 - Longo, Valter D. A1 - Dwaraka, Varun B. A1 - Gorbunova, Vera A1 - Acosta-Rodríguez, Victoria A. A1 - Sorrentino, Vincenzo A1 - Sebastiano, Vittorio A1 - Li, Wenbin A1 - Suh, Yousin A1 - Zhavoronkov, Alex A1 - Scheibye-Knudsen, Morten A1 - Bakula, Daniela T1 - Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity T2 - Aging Y1 - 2024 U6 - https://doi.org/10.18632/aging.206135 SN - 1945-4589 VL - 16 IS - 20 SP - 12955 EP - 12976 PB - Impact Journals, LLC ER -