Evaluation of DNA damage and cytotoxicity induced by triazole fungicide in cultured bovine lymphocytes

Schwarzbacherová, Viera; Šiviková, Katarı́na; Drážovská, Monika; Dianovský, Ján

doi:10.1080/00087114.2015.1032613

Cited by 20 publications

(7 citation statements)

References 35 publications

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“…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]. Additionally, Zhou et al [73] described apoptotic effects of tebuconazole (see Fig.…”

Section: Knowtox-case Studymentioning

confidence: 98%

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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Section: Knowtox-case Studymentioning

confidence: 98%

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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show abstract

“…The 1,2,4 triazolol could be a metabolite from the triazole antifungal agent used for controlling ascomycetes, fungi imperfecti, and basidiomycetes in a wide variety of crops, and its cytotoxicity was evaluated following many studies. , It was described to induce chromosomal aberrations, sister chromatid exchanges, and DNA fragmentation in cultured bovine lymphocytes and inhibit cytochrome P450 enzymes. Transcriptional analysis of liver tissues from the genomic studies of triazole antifungal agents suggests that these compounds induce constitutive androstane receptor and pregnane × receptor activation, CYP induction, oxidative stress, dysregulation of cholesterol biosynthesis, and alteration in cell signaling, cell growth, cell proliferation, and apoptosis pathways. , …”

Section: Discussionmentioning

confidence: 99%

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography–Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors

Louati,

Kolsi,

Kallel

et al. 2023

ACS Omega

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Pesticides are widely used, resulting in continuing human exposure with potential health impacts. Some exposures related to agricultural works have been associated with neurological disorders. Since the 2000s, the hypothesis of the role of pesticides in the occurrence of central nervous system (CNS) tumors has been better documented in the literature. However, the etiology of childhood brain cancers still remains largely unknown. The major objective of this work was to assess the potential role of pesticide exposure as a risk factor for CNS tumors based on questionnaires and statistical analysis of information collected from patients hospitalized in the Neurosurgery Department of the Habib Bourguiba Hospital Medium in Sfax, Tunisia, during the period from January 1, 2022, to May 31, 2023. It also aimed to develop a simple and rapid analytical method by the gas chromatography–mass spectrometry technique for the research traces of pesticide metabolites in some collected human brain tumor tissues in order to more emphasize our hypothesis for such a correlation between pesticide exposure and brain tumor development. Patients with a history of high-risk exposure were selected to conduct further analysis. Chemometric methods were adapted to discern intrinsic variation between pathological and control groups and ascertain effective separation with the identification of differentially expressed metabolites accountable for such variations. Three samples revealed traces of pesticide metabolites that were mostly detected at an early age. The histopathological diagnosis was medulloblastoma for a 10-year-old child and high-grade gliomas for 27- and 35-year-old adults. The bivariate analyses (odds ratio >1 and P value <5%) confirmed the great probability of developing cancer by an exposure case. The Cox proportional hazards model revealed the risk of carcinogenicity beyond the age of 50 as a long-term effect of pesticide toxicity. Our study supports the correlation between pesticide exposure and the risk of development of human brain tumors, suggesting that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased childhood brain tumor risk. This hypothesis was enhanced in identifying traces of metabolites from the carbamate insecticide class known for their neurotoxicity and others from pyridazinone, organochlorines (OCs), triazole fungicide, and N-nitroso compounds known for their carcinogenicity. The 2D-OXYBLOT analysis confirmed the neurotoxicity effect of insecticides to induce oxidative damage in CNS cells. Aldicarb was implicated in brain carcinogenicity confirmed by the identification of oxime metabolites in a stress degradation study. Revealing “aziridine” metabolites from the OC class may better emphasize the theory of detecting traces of pesticide metabolites at an early age. Overall, our findings lead to the recommendation of limiting the residential use of pesticides and the support of public health policies serving this objective that we need to be vigilant in the p...

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“…The triazoles group, by epoxiconazole and cyproconazole, did not present statistically significant effects. A second study, conducted by Schwarzbacherová and Šiviková (2015), evaluated the effect of a 24 and 48 exposure on bovine lymphocytes. The fungicide Prosaro® (tebuconazole / prothioconazole) was not considered toxic, except for the concentration of 30 μg mL -1 .…”

Section: Discussionmentioning

confidence: 99%

In vitro toxicological prospection of fungicides containing Difenoconazole or Tebuconazole as active ingredients

Trento¹,

César²,

Machado³

et al. 2022

Acta Biol. Par.

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Evaluation of DNA damage and cytotoxicity induced by triazole fungicide in cultured bovine lymphocytes

Cited by 20 publications

References 35 publications

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

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

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography–Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors

In vitro toxicological prospection of fungicides containing Difenoconazole or Tebuconazole as active ingredients

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