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  1. Article: Hazard Assessment of Benchmark Metal-Based Nanomaterials Through a Set of In Vitro Genotoxicity Assays.

    Vital, Nádia / Pinhão, Mariana / Yamani, Naouale El / Rundén-Pran, Elise / Louro, Henriqueta / Dušinská, Maria / Silva, Maria João

    Advances in experimental medicine and biology

    2022  Volume 1357, Page(s) 351–375

    Abstract: For safety assessment of nanomaterials (NMs), in vitro genotoxicity data based on well-designed 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, ... ...

    Abstract For safety assessment of nanomaterials (NMs), in vitro genotoxicity data based on well-designed 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.
    MeSH term(s) Animals ; Benchmarking ; Comet Assay/methods ; DNA ; DNA Damage ; Humans ; Mutagenicity Tests/methods ; Nanostructures/toxicity
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2022-05-18
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-88071-2_14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Correction to: Hazard Assessment of Benchmark Metal-Based Nanomaterials Through a Set of In Vitro Genotoxicity Assays.

    Vital, Nádia / Pinhão, Mariana / Yamani, Naouale El / Rundén-Pran, Elise / Louro, Henriqueta / Dušinská, Maria / Silva, Maria João

    Advances in experimental medicine and biology

    2022  Volume 1357, Page(s) C1

    Language English
    Publishing date 2022-07-25
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-88071-2_18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin a in human intestinal cells.

    Assunção, Ricardo / Pinhão, Mariana / Loureiro, Susana / Alvito, Paula / Silva, Maria João

    Toxicology letters

    2019  Volume 313, Page(s) 120–129

    Abstract: Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the ...

    Abstract Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.
    MeSH term(s) Caco-2 Cells ; DNA Damage ; Dose-Response Relationship, Drug ; Drug Synergism ; Electric Impedance ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Models, Biological ; Ochratoxins/toxicity ; Oxidative Stress/drug effects ; Patulin/toxicity ; Permeability
    Chemical Substances Ochratoxins ; ochratoxin A (1779SX6LUY) ; Patulin (95X2BV4W8R)
    Language English
    Publishing date 2019-06-15
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article
    ZDB-ID 433788-8
    ISSN 1879-3169 ; 0378-4274
    ISSN (online) 1879-3169
    ISSN 0378-4274
    DOI 10.1016/j.toxlet.2019.06.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Biological impact of metal nanomaterials in relation to their physicochemical characteristics.

    Louro, Henriqueta / Saruga, Andreia / Santos, Joana / Pinhão, Mariana / Silva, Maria João

    Toxicology in vitro : an international journal published in association with BIBRA

    2019  Volume 56, Page(s) 172–183

    MeSH term(s) A549 Cells ; Barium Sulfate/chemistry ; Barium Sulfate/toxicity ; Cell Survival/drug effects ; Cerium/chemistry ; Cerium/toxicity ; Comet Assay ; Humans ; Micronucleus Tests ; Nanostructures/chemistry ; Nanostructures/toxicity ; Titanium/chemistry ; Titanium/toxicity
    Chemical Substances titanium dioxide (15FIX9V2JP) ; Barium Sulfate (25BB7EKE2E) ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y) ; Titanium (D1JT611TNE)
    Language English
    Publishing date 2019-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 639064-x
    ISSN 1879-3177 ; 0887-2333
    ISSN (online) 1879-3177
    ISSN 0887-2333
    DOI 10.1016/j.tiv.2019.01.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Corrigendum to "Biological impact of metal nanomaterials in relation to their physicochemical characteristics" [Toxicol in Vitro. 2019 Jan 29;56:172-183].

    Louro, Henriqueta / Saruga, Andreia / Santos, Joana / Pinhão, Mariana / Silva, Maria João

    Toxicology in vitro : an international journal published in association with BIBRA

    2019  Volume 59, Page(s) 323

    Language English
    Publishing date 2019-02-16
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 639064-x
    ISSN 1879-3177 ; 0887-2333
    ISSN (online) 1879-3177
    ISSN 0887-2333
    DOI 10.1016/j.tiv.2019.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Evaluation of the cytotoxic and genotoxic effects of benchmark multi-walled carbon nanotubes in relation to their physicochemical properties.

    Louro, Henriqueta / Pinhão, Mariana / Santos, Joana / Tavares, Ana / Vital, Nádia / Silva, Maria João

    Toxicology letters

    2016  Volume 262, Page(s) 123–134

    Abstract: To contribute with scientific evidence to the grouping strategy for the safety assessment of multi-walled carbon nanotubes (MWCNTs), this work describes the investigation of the cytotoxic and genotoxic effects of four benchmark MWCNTs in relation to ... ...

    Abstract To contribute with scientific evidence to the grouping strategy for the safety assessment of multi-walled carbon nanotubes (MWCNTs), this work describes the investigation of the cytotoxic and genotoxic effects of four benchmark MWCNTs in relation to their physicochemical characteristics, using two types of human respiratory cells. The cytotoxic effects were analysed using the clonogenic assay and replication index determination. A 48h-exposure of cells revealed that NM-401 was the only cytotoxic MWCNT in both cell lines, but after 8-days exposure, the clonogenic assay in A549 cells showed cytotoxic effects for all the tested MWCNTs. Correlation analysis suggested an association between the MWCNTs size in cell culture medium and cytotoxicity. No induction of DNA damage was observed after any MWCNTs in any cell line by the comet assay, while the micronucleus assay revealed that both NM-401 and NM-402 were genotoxic in A549 cells. NM-401 and NM-402 are the two longest MWCNTs analyzed in this work, suggesting that length may be determinant for genotoxicity. No induction of micronuclei was observed in BBEAS-2Beas-2B cell line and the different effect in both cell lines is explained in view of the size-distribution of MWCNTs in the cell culture medium, rather than cell's specificities.
    MeSH term(s) Benchmarking ; Cell Line ; Cell Survival/drug effects ; Chemical Phenomena ; Comet Assay ; DNA Damage ; Humans ; Micronucleus Tests ; Mutagens/toxicity ; Nanotubes, Carbon/chemistry ; Nanotubes, Carbon/toxicity ; Particle Size
    Chemical Substances Mutagens ; Nanotubes, Carbon
    Language English
    Publishing date 2016-11-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 433788-8
    ISSN 1879-3169 ; 0378-4274
    ISSN (online) 1879-3169
    ISSN 0378-4274
    DOI 10.1016/j.toxlet.2016.09.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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