Evaluation of cytotoxic and genotoxic activity of fungicide formulation Tango® Super in bovine lymphocytes

Schwarzbacherová, Viera; Wnuk, Maciej; Lewińska, Anna; Potocki, Leszek; Żebrowski, Jacek; Koziorowski, Marek; Holečková, Beáta; Šiviková, Katarı́na; Dianovský, Ján

doi:10.1016/j.envpol.2016.09.057

Cited by 23 publications

(10 citation statements)

References 65 publications

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“…It has been demonstrated that antifungal agents such as amphotericin B and azoles trigger common cell-death pathways causing oxidative damage in fungi such as Candida albicans , Saccharomyces cerevisiae or Cryptococcus gattii [ 63 ]. Supporting our results, it was found that Tango ® [ 33 ] and a thiacloprid-based insecticide induced oxidative stress in bovine lymphocytes in other studies [ 64 ]. It appears that modulation of ergosterol synthesis caused by the twin-component fungicide (fenpropimorph and epoxiconazole) in all studied Candida strains could play a key role in the adaptation of cells during oxidative stress [ 65 ].…”

Section: Discussionsupporting

confidence: 90%

“…After 24 h Candida cell treatment with commercial pesticides and their active ingredients, the mitochondrial superoxide level (MitoTracker ® Red CM H2XRos, Thermo Fisher Scientific, Waltham, MA, USA.) was assessed as previously described [ 33 ].The integrated fluorescence density was measured using a Tecan Scientific microplate reader equipped with monochromator optics at excitation wavelength 579 nm and emission 599 nm.…”

Section: Methodsmentioning

confidence: 99%

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Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

Potocki

Baran

Oklejewicz

et al. 2020

Genes

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The effects of triazole fungicide Tango® (epoxiconazole) and two neonicotinoid insecticide formulations Mospilan® (acetamiprid) and Calypso® (thiacloprid) were investigated in Candida albicans and three non-albicans species Candida pulcherrima, Candida glabrata and Candida tropicalis to assess the range of morphological, metabolic and genetic changes after their exposure to pesticides. Moreover, the bioavailability of pesticides, which gives us information about their metabolization was assessed using gas chromatography-mass spectrophotometry (GC-MS). The tested pesticides caused differences between the cells of the same species in the studied populations in response to ROS accumulation, the level of DNA damage, changes in fatty acids (FAs) and phospholipid profiles, change in the percentage of unsaturated to saturated FAs or the ability to biofilm. In addition, for the first time, the effect of tested neonicotinoid insecticides on the change of metabolic profile of colony cells during aging was demonstrated. Our data suggest that widely used pesticides, including insecticides, may increase cellular diversity in the Candida species population-known as clonal heterogeneity-and thus play an important role in acquiring resistance to antifungal agents.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

Potocki

Baran

Oklejewicz

et al. 2020

Genes

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“…Also, in literature, evidence for cytotoxicity and cell cycle inhibition by triazole fungicides or mixtures containing such is given. For instance, Schwarzbacherova et al reported cytotoxic and genotoxic effects, such as reduced cell viability, decreased cell proliferation, and apoptosis of bovine lymphocytes induced by fungicides [71]. In another study, they found bovine lymphocytes proliferation inhibited by a mixture of two conazole fungicides [72].…”

Section: Knowtox-case Studymentioning

confidence: 99%

KnowTox: pipeline and case study for confident prediction of potential toxic effects of compounds in early phases of development

Morger¹,

Mathea²,

Achenbach³

et al. 2020

J Cheminform

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Risk assessment of newly synthesised chemicals is a prerequisite for regulatory approval. In this context, in silico methods have great potential to reduce time, cost, and ultimately animal testing as they make use of the ever-growing amount of available toxicity data. Here, KnowTox is presented, a novel pipeline that combines three different in silico toxicology approaches to allow for confident prediction of potentially toxic effects of query compounds, i.e. machine learning models for 88 endpoints, alerts for 919 toxic substructures, and computational support for read-across. It is mainly based on the ToxCast dataset, containing after preprocessing a sparse matrix of 7912 compounds tested against 985 endpoints. When applying machine learning models, applicability and reliability of predictions for new chemicals are of utmost importance. Therefore, first, the conformal prediction technique was deployed, comprising an additional calibration step and per definition creating internally valid predictors at a given significance level. Second, to further improve validity and information efficiency, two adaptations are suggested, exemplified at the androgen receptor antagonism endpoint. An absolute increase in validity of 23% on the in-house dataset of 534 compounds could be achieved by introducing KNNRegressor normalisation. This increase in validity comes at the cost of efficiency, which could again be improved by 20% for the initial ToxCast model by balancing the dataset during model training. Finally, the value of the developed pipeline for risk assessment is discussed using two in-house triazole molecules. Compared to a single toxicity prediction method, complementing the outputs of different approaches can have a higher impact on guiding toxicity testing and de-selecting most likely harmful development-candidate compounds early in the development process.

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“…The fungicide did not induce micronuclei production, but the cell proliferation was significantly decreased [10,42].…”

Section: Slide Scoring and Analysismentioning

confidence: 94%

Micronucleus Assay in Environmental Biomonitoring

et al. 2020

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AbstractNowadays many chemicals are widely used in agriculture to ensure high crop yields or in veterinary/human medicine to cure diseases. After their improper usage they may contaminate the environment, persist in it and adversely affect both the target and/or the non-target organisms. One of the ways to detect the occurrence of chemicals in the environment is to assess their impact on aquatic and farm animals; both are directly or indirectly exposed via their feed and water. The micronucleus assay is a standardly used cytogenetic test for the simultaneous detection of clastogenic and aneugenic agents. Additionally, cytotoxic effects are also assessed by analysing the proliferation changes using the cytokinesis-blocked proliferation index. The occurrence of micronuclei is analysed in many types of cells like the peripheral blood cells, bone marrow or cell lines according to standards for micronuclei detection. The analysis of published results has shown that the micronucleus assay is, together with the chromosomal aberration test, one of the most often used test in genotoxicity assessment. Its results have contributed to reassessing the use of multiple chemicals available on the market. Moreover, it is a compulsory test before approving the chemical/ pesticide for the market.

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Evaluation of cytotoxic and genotoxic activity of fungicide formulation Tango® Super in bovine lymphocytes

Cited by 23 publications

References 65 publications

Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

KnowTox: pipeline and case study for confident prediction of potential toxic effects of compounds in early phases of development

Micronucleus Assay in Environmental Biomonitoring

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