Browsing by Author "Žegura, Bojana"
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- DNA damage in circulating leukocytes measured with the comet assay may predict the risk of deathPublication . Bonassi, Stefano; Ceppi, Marcello; Møller, Peter; Azqueta, Amaya; Milić, Mirta; Neri, Monica; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine A.S.; Teixeira, João Paulo; Bruzzone, Marco; Da Silva, Juliana; Benedetti, Danieli; Cavallo, Delia; Ursini, Cinzia Lucia; Giovannelli, Lisa; Moretti, Silvia; Riso, Patrizia; Del Bo’, Cristian; Russo, Patrizia; Dobrzyńska, Malgorzata; Goroshinskaya, Irina A.; Surikova, Ekaterina I.; Staruchova, Marta; Barančokova, Magdalena; Volkovova, Katarina; Kažimirova, Alena; Smolkova, Bozena; Laffon, Blanca; Valdiglesias, Vanessa; Pastor, Susana; Marcos, Ricard; Hernández, Alba; Gajski, Goran; Spremo-Potparević, Biljana; Živković, Lada; Boutet-Robinet, Elisa; Perdry, Hervé; Lebailly, Pierre; Perez, Carlos L.; Basaran, Nursen; Nemeth, Zsuzsanna; Safar, Anna; Dusinska, Maria; Collins, Andrew; Anderson, Diana; Andrade, Vanessa; Pereira, Cristiana Costa; Costa, Solange; Gutzkow, Kristine B.; Ladeira, Carina; Moretti, Massimo; Costa, Carla; Orlow, Irene; Rojas, Emilio; Pourrut, Bertrand; Kruszewski, Marcin; Knasmueller, Siegfried; Shaposhnikov, Sergey; Žegura, Bojana; Stopper, HelgaThe comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.
- Exploring BPA alternatives - Environmental levels and toxicity reviewPublication . Adamovsky, Ondrej; Groh, Ksenia J.; Białk-Bielińska, Anna; Escher, Beate I.; Beaudouin, R.; Mora Lagares, Liadys; Tollefsen, Knut Erik; Fenske, Martina; Mulkiewicz, Ewa; Creusot, Nicolas; Sosnowska, Anita; Loureiro, Susana; Beyer, Jonny; Repetto, Guillermo; Štern, Alja; Lopes, Isabel; Monteiro, Marta; Zikova-Kloas, Andrea; Eleršek, Tina; Vračko, Marjan; Zdybel, Szymon; Puzyn, Tomasz; Koczur, Weronika; Ebsen Morthorst, Jane; Holbech, Henrik; Carlsson, Gunnar; Örn, Stefan; Herrero, Óscar; Siddique, Ayesha; Liess, Matthias; Braun, Georg; Srebny, Vanessa; Žegura, Bojana; Hinfray, Nathalie; Brion, François; Knapen, Dries; Vandeputte, Ellen; Stinckens, Evelyn; Vergauwen, Lucia; Behrendt, Lars; Silva, Maria João; Blaha, Ludek; Kyriakopoulou, KaterinaBisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.
- Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human healthPublication . Louro, Henriqueta; Vettorazzi, Ariane; López de Cerain, Adela; Spyropoulou, Anastasia; Solhaug, Anita; Straumfors, Anne; Behr, Anne-Cathrin; Mertens, Birgit; Žegura, Bojana; Fæste, Christiane Kruse; Ndiaye, Dieynaba; Spilioti, Eliana; Varga, Elisabeth; Dubreil, Estelle; Borsos, Eszter; Crudo, Francesco; Eriksen, Gunnar Sundstøl; Snapkow, Igor; Henri, Jérôme; Sanders, Julie; Machera, Kyriaki; Gaté, Laurent; Le Hegarat, Ludovic; Novak, Matjaž; Smith, Nicola M.; Krapf, Solveig; Hager, Sonja; Fessard, Valérie; Kohl, Yvonne; Silva, Maria João; Dirven, Hubert; Dietrich, Jessica; Marko, DorisFungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.
- Hazard identification and characterization of leachable chemicals from plastic products – a new PARC projectPublication . Dirven, Hubert; Bogusz, Aleksandra; Hans Bouwmeester; Busch, Mathias; Duflos, Guillaume; Eriksen, Gunnar S.; Fardilha, Margarida; Flores-Gomez, Daniela; Franko, Nina; Gaté, Laurent; Guichard, Yves; Silva, Maria Joao; Kamstra, Jorke H.; Kasiotis, Konstantinos M.; Kim, Sunmi; Kim, Young Jun; Kim, Youngsam; van der Koogh, Elise; Loureiro, Susana; Louro, Henriqueta; Machera, Kyriaki; Pieters, Raymond H. H.; Spyropoulou, Anastasia; Tzanetou, Evangelia N.; Malheiro, Catarina; Ravnjak, Tim; Repetto, Guillermo; Rivière, Gilles; Ryu, Chang Seon; Papadopoulou, Evgenia Anna; Aliferis, Konstantinos A.; Solhaug, Anita; Sollner Dolenc, Marija; Štampar, Martina; Tavares, Ana M.; Tollefsen, Knut Erik; Ventura, Célia; Walkowiak, Radoslaw; Zobl, Walter; Žegura, Bojana; Snapkow, Igor; Herzke, DorteA recent study has suggested that plastics may contain more than 16,000 chemicals, including additives, processing aids, starting substances, intermediates and Non-Intentionally Added Substances. Plastic chemicals are released throughout the plastic life cycle, from production, use, disposal and recycling. Most of these chemicals have not been studied for potential hazardous properties for humans and in the environment. To refine the risk assessment of these leachable chemicals, additional hazard data are needed. The PlasticLeach project within the EU co-funded Partnership for the Assessment of Risks from Chemicals (PARC) aims to address this data gap by screening several plastic products in daily use. Leachates will be prepared from a number of these plastic items, and these chemical mixtures will be further tested using several test guideline compliant assays and New Approach Methodologies covering both human health and environmental endpoints. The most toxic leachates will be characterized using a non-targeted analysis pipeline to identify chemicals in the leachate. When single chemicals of concern are identified, these will be further tested to determine hazardous properties and identify the respective potency factors to better understand their specific hazard profiles. A tiered approach for hazard testing will be followed. The experimental work will be complemented by toxicological profiling, using publicly available toxicity databases and tools, including Artificial Intelligence tools that cover both human and environmental endpoints. A comprehensive array of endpoints, including cytotoxicity, endocrine disruption, genotoxicity, immunotoxicity, reproductive toxicity and effects related to ecotoxicity will be evaluated. In this paper, we outline the plastic products to be tested and the battery of assays that will be used to identify hazards relevant to both human health and the environment. Data generated from approaches will be reported using standardized formats, stored within a centralized repository, and harmonized to adhere to the FAIR data principles (Findable, Accessible, Interoperable, and Reusable). This integrated strategy will not only advance our understanding of the risks associated with plastic-derived chemicals but will also provide critical support for regulatory decision-making and facilitate the development of safer, and more ecofriendly plastic materials in the future.
- Measuring DNA modifications with the comet assay: a compendium of protocolsPublication . Collins, Andrew; Møller, Peter; Gajski, Goran; Vodenková, Soňa; Abdulwahed, Abdulhadi; Anderson, Diana; Bankoglu, Ezgi Eyluel; Bonassi, Stefano; Boutet-Robinet, Elisa; Brunborg, Gunnar; Chao, Christy; Cooke, Marcus S.; Costa, Carla; Costa, Solange; Dhawan, Alok; de Lapuente, Joaquin; Bo’, Cristian Del; Dubus, Julien; Dusinska, Maria; Duthie, Susan J.; Yamani, Naouale El; Engelward, Bevin; Gaivão, Isabel; Giovannelli, Lisa; Godschalk, Roger; Guilherme, Sofia; Gutzkow, Kristine B.; Habas, Khaled; Hernández, Alba; Herrero, Oscar; Isidori, Marina; Jha, Awadhesh N.; Knasmüller, Siegfried; Kooter, Ingeborg M.; Koppen, Gudrun; Kruszewski, Marcin; Ladeira, Carina; Laffon, Blanca; Larramendy, Marcelo; Hégarat, Ludovic Le; Lewies, Angélique; Lewinska, Anna; Liwszyc, Guillermo E.; de Cerain, Adela López; Manjanatha, Mugimane; Marcos, Ricard; Milić, Mirta; de Andrade, Vanessa Moraes; Moretti, Massimo; Muruzabal, Damian; Novak, Matjaž; Oliveira, Rui; Olsen, Ann-Karin; Owiti, Norah; Pacheco, Mário; Pandey, Alok K.; Pfuhler, Stefan; Pourrut, Bertrand; Reisinger, Kerstin; Rojas, Emilio; Rundén-Pran, Elise; Sanz-Serrano, Julen; Shaposhnikov, Sergey; Sipinen, Ville; Smeets, Karen; Stopper, Helga; Teixeira, João Paulo; Valdiglesias, Vanessa; Valverde, Mahara; van Acker, Frederique; van Schooten, Frederik-Jan; Vasquez, Marie; Wentzel, Johannes F.; Wnuk, Maciej; Wouters, Annelies; Žegura, Bojana; Zikmund, Tomas; Langie, Sabine A.S.; Azqueta, AmayaThe comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA-DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility.
- The comet assay in animal models: From bugs to whales – (Part 1 Invertebrates)Publication . Gajski, Goran; Žegura, Bojana; Ladeira, Carina; Pourrut, Bertrand; Del Bo’, Cristian; Novak, Matjaž; Sramkova, Monika; Milić, Mirta; Gutzkow, Kristine Bjerve; Costa, Solange; Dusinska, Maria; Brunborg, Gunnar; Collins, AndrewThe comet assay, also called single cell gel electrophoresis, is a sensitive, rapid and low-cost technique for quantifying and analysing DNA damage and repair at the level of individual cells. The assay itself can be applied on virtually any cell type derived from different organs and tissues of eukaryotic organisms. Although it is mainly used on human cells, the assay has applications also in the evaluation of DNA damage in yeast, plant and animal cells. Therefore, the purpose of this review is to give an extensive overview on the usage of the comet assay in animal models from invertebrates to vertebrates, covering both terrestrial and water biota. The comet assay is used in a variety of invertebrate species since they are regarded as interesting subjects in ecotoxicological research due to their significance in ecosystems. Hence, the first part of the review (Part 1) will discuss the application of the comet assay in invertebrates covering protozoans, platyhelminthes, planarians, cnidarians, molluscs, annelids, arthropods and echinoderms. Besides a large number of animal species, the assay is also performed on a variety of cells, which includes haemolymph, gills, digestive gland, sperm and embryo cells. The mentioned cells have been used for the evaluation of a broad spectrum of genotoxic agents both in vitro and in vivo. Moreover, the use of invertebrate models and their role from an ecotoxicological point of view will also be discussed as well as the comparison of the use of the comet assay in invertebrate and human models. Since the comet assay is still developing, its increasing potential in assessing DNA damage in animal models is crucial especially in the field of ecotoxicology and biomonitoring at the level of different species, not only humans.
- The comet assay in animal models: From bugs to whales – (Part 2 Vertebrates)Publication . Gajski, Goran; Žegura, Bojana; Ladeira, Carina; Novak, Matjaž; Sramkova, Monika; Pourrut, Bertrand; Del Bo’, Cristian; Milić, Mirta; Gutzkow, Kristine Bjerve; Costa, Solange; Dusinska, Maria; Brunborg, Gunnar; Collins, AndrewThe comet assay has become one of the methods of choice for the evaluation and measurement of DNA damage. It is sensitive, quick to perform and relatively affordable for the evaluation of DNA damage and repair at the level of individual cells. The comet assay can be applied to virtually any cell type derived from different organs and tissues. Even though the comet assay is predominantly used on human cells, the application of the assay for the evaluation of DNA damage in yeast, plant and animal cells is also quite high, especially in terms of biomonitoring. The present extensive overview on the usage of the comet assay in animal models will cover both terrestrial and water environments. The first part of the review was focused on studies describing the comet assay applied in invertebrates. The second part of the review, (Part 2) will discuss the application of the comet assay in vertebrates covering cyclostomata, fishes, amphibians, reptiles, birds and mammals, in addition to chordates that are regarded as a transitional form towards vertebrates. Besides numerous vertebrate species, the assay is also performed on a range of cells, which includes blood, liver, kidney, brain, gill, bone marrow and sperm cells. These cells are readily used for the evaluation of a wide spectrum of genotoxic agents both in vitro and in vivo. Moreover, the use of vertebrate models and their role in environmental biomonitoring will also be discussed as well as the comparison of the use of the comet assay in vertebrate and human models in line with ethical principles. Although the comet assay in vertebrates is most commonly used in laboratory animals such as mice, rats and lately zebrafish, this paper will only briefly review its use regarding laboratory animal models and rather give special emphasis to the increasing usage of the assay in domestic and wildlife animals as well as in various ecotoxicological studies.