Genotoxicity of zinc oxide nanoparticles: an<i>in vivo</i>and<i>in silico</i>study

Cardozo, Tatiane Rocha; Carli, Raíne Fogliati de; Seeber, Allan; Flores, Wladimir Hernandez; Rosa, Jordana Ariane Nunes da; Kotzal, Queila Susana Gambim; Lehmann, Maurı́cio; Silva, Fernanda Rabaioli da; Dihl, Rafael Rodrigues

doi:10.1039/c8tx00255j

Cited by 21 publications

(8 citation statements)

References 48 publications

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“…Gold nanoparticles --20-30 µg/mL, all of doses inconclusive in ST cross, whereby all of concentrations lack genotoxicity in HB cross [113] Iron oxide nanoparticle (<50 nm) + nd 1-10 mM, inconclusive at 2 and 5 mM, positive at 1 and 10 mM [114] Iron oxide nanoparticle (<100 nm) -nd 1-10 mM, inconclusive at 1 mM and lack genotoxicity 2-10 mM [114] Iron nanoparticles -nd 0.1-10 mM, all concentrations lack genotoxicity [115] Nickel oxide nanoparticles + + [116] nd-not determined, (-)-negative, and (+)-positive.…”

Section: Results In Hb Cross Range Of Treated Doses and Remarksmentioning

confidence: 99%

Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing—A Review

Pitchakarn

Inthachat

Karinchai

et al. 2021

IJMS

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Genomic instability, one of cancer’s hallmarks, is induced by genotoxins from endogenous and exogenous sources, including reactive oxygen species (ROS), diet, and environmental pollutants. A sensitive in vivo genotoxicity test is required for the identification of human hazards to reduce the potential health risk. The somatic mutation and recombination test (SMART) or wing spot test is a genotoxicity assay involving Drosophila melanogaster (fruit fly) as a classical, alternative human model. This review describes the principle of the SMART assay in conjunction with its advantages and disadvantages and discusses applications of the assay covering all segments of health-related industries, including food, dietary supplements, drug industries, pesticides, and herbicides, as well as nanoparticles. Chemopreventive strategies are outlined as a global health trend for the anti-genotoxicity of interesting herbal extract compounds determined by SMART assay. The successful application of Drosophila for high-throughput screening of mutagens is also discussed as a future perspective.

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Section: Results In Hb Cross Range Of Treated Doses and Remarksmentioning

confidence: 99%

Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing—A Review

Pitchakarn

Inthachat

Karinchai

et al. 2021

IJMS

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“…Elevated levels of reactive oxygen species (ROS) can often lead to decreased cell viability as previously shown [ 25 , 26 ]. ROS are natural byproducts of cellular oxidative metabolism and play an important role in cell survival, cell death, differentiation, cell signaling, and inflammation-related factor production [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…It appears that a similar DNA damage response occurs as treated with ZnO in different organisms. For example, in a recent study, CCNA2 was also upregulated in D. melanogaster after ZnO treatment [ 26 ]. The upregulation of the p53 pathway in ZnO-treated cells is highly consistent with the increased late apoptosis observed in our apoptosis results ( Figure 8 ).…”

Section: Discussionmentioning

confidence: 99%

Non-ROS-Mediated Cytotoxicity of ZnO and CuO in ML-1 and CA77 Thyroid Cancer Cell Lines

Peters

Weaver

Monahan

et al. 2023

IJMS

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Metal oxide nanoparticles (MONPs) are widely used in agriculture and food development but there is little understanding of how MONPs, including ZnO, CuO, TiO2, and SnO2, impact human health and the environment. Our growth assay revealed that none of these (up to 100 µg/mL) negatively affect viability in the budding yeast, Saccharomyces cerevisiae. In contrast, both human thyroid cancer cells (ML-1) and rat medullary thyroid cancer cells (CA77) displayed a significant reduction in cell viability with the treatment of CuO and ZnO. The production of reactive oxygen species (ROS) in these cell lines, when treated with CuO and ZnO, was found to be not significantly altered. However, levels of apoptosis with ZnO and CuO were increased, which led us to conclude that the decreased cell viability is mainly caused by non-ROS-mediated cell death. Consistently, data from our RNAseq studies identified differentially regulated pathways associated with inflammation, Wnt, and cadherin signaling across both cell lines, ML-1, and CA77, after ZnO or CuO MONP treatment. Results from gene studies further support non-ROS-mediated apoptosis being the main factor behind decreased cell viability. Together, these findings provide unique evidence that the apoptosis in response to treatment of CuO and ZnO in these thyroid cancer cells was not mainly due to oxidative stress, but to the alteration of a range of signal cascades that promotes cell death.

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“…Genotoxic responses for ZnO-NP are closely associated with the release of the Zn 2 + ions that raise the levels of intracellular EROS and induce lipid peroxidation, damage to membranes, and oxidative stress in other bioassays (Ahamed et al, 2013;Cardozo et al, 2019;Choi & Choy, 2014;Magdolenova et al, 2014;Pan et al, 2010;Sizochenko et al, 2019;Yang et al, 2009). The solution of ZnO-NP in neutral pH induced the highest value of mutagenesis observed in the assays, followed by NiO-NP in the same pH, in the TA102 strain (Table 2 and Figure caused even more reversion in a strain of E. coli sensitive to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Lowering the pH leads to the disaggregation of NiO and ZnO nanoparticles and modifies the mutagenic response

Pescke,

de Oliveira Rozino,

Zenato

et al. 2023

J of Applied Toxicology

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In a changing environmental scenario, acid rain can have a significant impact on aquatic ecosystems. Acidification is known to produce corrosion in metals, hence increasing their harmful effects on the environment, organisms and human health. The prevalent use of metallic nanoparticles (NPs) in everyday products raises concerns regarding exposure and nanotoxicity even in these acidified conditions. We thus report on the cytotoxic and genotoxic potential of nickel oxide (NiO‐NP) and zinc oxide (ZnO‐NP) NPs when suspended in aqueous media in light of pH variations (7.5 and 5). A modified microsuspension method of the Salmonella/microsome assay was adopted, and strains (TA97a, TA98, TA100, TA102) were exposed to NPs (10–1280 μg/plate) with and without a metabolization fraction. The acidic condition favored disaggregation and caused a decrease in NPs size. Mutagenicity was observed in all samples and different strains, with greater DNA base pair substitution damage (TA100 and TA102), but extrinsic conditions (pH) suggest different action mechanisms of NiO‐NP and ZnO‐NP on genetic content. Mutagenic activity was found to increase upon metabolic activation (TA98, TA100, and TA102) demonstrating the bioactivity of NiO‐NP and ZnO‐NP in relation to metabolites generated by the mammalian p450 system in vitro. Modifications in the Salmonella assay methodology increased cell exposure time. The observed responses recommend this modified assay as one of the methodologies of choice for nanoecotoxicological evaluation. These findings emphasize the significance of incorporating the environmental context when evaluating the toxicity of metal‐based NPs.

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Genotoxicity of zinc oxide nanoparticles: anin vivoandin silicostudy

Abstract: Zinc oxide (ZnO) NPs are being used worldwide in consumer products and industrial applications.

Cited by 21 publications

References 48 publications

Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing—A Review

Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing—A Review

Non-ROS-Mediated Cytotoxicity of ZnO and CuO in ML-1 and CA77 Thyroid Cancer Cell Lines

Lowering the pH leads to the disaggregation of NiO and ZnO nanoparticles and modifies the mutagenic response

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