Browsing by Author "Dušinská, Maria"
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- Contribution to the hazard assessment of benchmark metallic nanomaterials through a set of in vitro genotoxicity assaysPublication . Vital, Nádia; El Yamani, Naouale; Pinhão, Mariana; Rúden-Pra, Elise; Louro, Henriqueta; Dušinská, Maria; Silva, Maria JoãoMetallic nanomaterials are among the most commonly applied manufactured nanomaterials (NM). Regardless of the considerable efforts to assess their safety, the presently available data do not allow for general and consistent conclusions. Moreover, the validity of the classical in vitro testing systems for NMs hazard assessment has been questioned and needs confirmation. In the present study, the toxicity of three benchmark metallic NMs, including two insoluble NMs - titanium (NM-100) and cerium (NM-212) dioxides - and soluble silver nanorods/wires (NM-302) was investigated. A panel of in vitro genotoxicity tests that analyze different endpoints was applied and the physico-chemical properties of each NM were considered.
- Contribution to the hazard assessment of benchmark metallic nanomaterials through a set of in vitro genotoxicity assaysPublication . Vital, Nádia; El Yamani, Naouale; Pinhão, Mariana; Rúden-Pra, Elise; Louro, Henriqueta; Dušinská, Maria; Silva, Maria JoãoBackground and Aim: Metall-based nanomaterials (NMs) are among the most commonly applied manufactured nanomaterials (NM). Regardless of the considerable efforts to assess their safety, the presently available data do not allow for general and consistent conclusions. Moreover, the validity of the classical in vitro testing systems for NMs hazard assessment has been questioned and needs confirmation. The present study aimed at evaluating the toxicity of three benchmark metallic NMs - titanium dioxide (NM-100),cerium dioxide (NM-212) and nanosilver - with different physicochemical properties, using a battery of in vitro genotoxicity assays, in an attempt to characterize their toxicity profile.
- Hazard Assessment of Benchmark Metal-Based Nanomaterials Through a Set of In Vitro Genotoxicity AssaysPublication . Vital, Nádia; Pinhão, Mariana; Yamani, Naouale El; Rundén-Pran, Elise; Louro, Henriqueta; Dušinská, Maria; Silva, Maria JoãoFor safety assessment of nanomaterials (NMs), in vitro genotoxicity data based on welldesigned experiments is required. Metal-based NMs are amongst the most used in consumer products. In this chapter, we report results for three metal-based NMs, titanium dioxide (NM- 100), cerium dioxide (NM-212) and silver (NM-302) in V79 cells, using a set of in vitro genotoxicity assays covering different endpoints: the medium-throughput comet assay and its modified version (with the enzyme formamidopyrimidine DNA glycosylase, Fpg), measuring DNA strand beaks (SBs) and oxidized purines, respectively; the micronucleus (MN) assay, assessing chromosomal damage; and the Hprt gene mutation test. The results generated by this test battery showed that all NMs displayed genotoxic potential. NM-100 induced DNA breaks, DNA oxidation damage and point mutations but not chromosome instability. NM-212 increased the level of DNA oxidation damage, point mutations and increased the MN frequency at the highest concentration tested. NM-302 was moderately cytotoxic and induced gene mutations, but not DNA or chromosome damage. In conclusion, the presented in vitro genotoxicity testing strategy allowed the identification of genotoxic effects caused by three different metal-based NMs, raising concern as to their impact on human health. The results support the use of this in vitro test battery for the genotoxicity assessment of NMs, reducing the use of more expensive, time-consuming and ethically demanding in vivo assays, in compliance with the 3 R’s.
- The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confoundersPublication . Milić, Mirta; Ceppi, Marcello; Bruzzone, Marco; Azqueta, Amaya; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine; Møller, Peter; Teixeira, João Paulo; Alija, Avdulla; Anderson, Diana; Andrade, Vanessa; Andreoli, Cristina; Asllani, Fisnik; Bangkoglu, Ezgi Eyluel; Barančoková, Magdalena; Basaran, Nursen; Boutet-Robinet, Elisa; Buschini, Annamaria; Cavallo, Delia; Costa Pereira, Cristiana; Costa, Carla; Costa, Solange; Da Silva, Juliana; Del Boˊ, Cristian; Dimitrijević Srećković, Vesna; Djelić, Ninoslav; Dobrzyńska, Malgorzata; Duračková, Zdenka; Dvořáková, Monika; Gajski, Goran; Galati, Serena; García Lima, Omar; Giovannelli, Lisa; Goroshinskaya, Irina A.; Grindel, Annemarie; Gutzkow, Kristine B.; Hernández, Alba; Hernández, Carlos; Holven, Kirsten B.; Ibero-Baraibar, Idoia; Ottestad, Inger; Kadioglu, Ela; Kažimirová, Alena; Kuznetsova, Elena; Ladeira, Carina; Laffon, Blanca; Lamonaca, Palma; Lebailly, Pierre; Louro, Henriqueta; Mandina Cardoso, Tania; Marcon, Francesca; Marcos, Ricard; Moretti, Massimo; Moretti, Silvia; Najafzadeh, Mojgan; Nemeth, Zsuzsanna; Neri, Monica; Novotna, Bozena; Orlow, Irene; Paduchova, Zuzana; Pastor, Susana; Perdry, Hervé; Spremo-Potparević, Biljana; Ramadhani, Dwi; Riso, Patrizia; Rohr, Paula; Rojas, Emilio; Rossner, Pavel; Safar, Anna; Sardas, Semra; Silva, Maria João; Sirota, Nikolay; Smolkova, Bozena; Staruchova, Marta; Stetina, Rudolf; Stopper, Helga; Surikova, Ekaterina I.; Ulven, Stine M.; Ursini, Cinzia Lucia; Valdiglesias, Vanessa; Valverde, Mahara; Vodicka, Pavel; Volkovova, Katarina; Wagner, Karl-Heinz; Živković, Lada; Dušinská, Maria; Collins, Andrew R.; Bonassi, StefanoThe alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.