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Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs

2023-10Artigo científico Acesso aberto
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dc.contributor.authorLadeira, Carina
dc.contributor.authorAraújo, Rúben
dc.contributor.authorRamalhete, Luís
dc.contributor.authorTeixeira, Hélder
dc.contributor.authorCalado, Cecília R.C.
dc.contributor.institutionComprehensive Health Research Centre (CHRC) - Pólo ENSP
dc.contributor.institutionCentro de Investigação em Saúde Pública (CISP/PHRC)
dc.contributor.institutionEscola Nacional de Saúde Pública (ENSP)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionComprehensive Health Research Centre (CHRC) - pólo NMS
dc.contributor.pblElsevier
dc.date.accessioned2024-05-01T01:09:00Z
dc.date.available2024-05-01T01:09:00Z
dc.date.issued2023-10
dc.descriptionFunding Information: This work was supported by Instituto Politécnico de Lisboa under grant IDI&CA/IPL/2021/PLASCOGEN_ESTeSL, IDI&CA/IPL/2017/GenTox/ESTeSL, and by the Fundação para a Ciência e a Tecnologia, Portugal, under grant DSAIPA/DS/0117/2020. The human biomonitoring had financial support given by Portuguese Authority of Working Conditions (Project reference: 036APJ/09). Funding Information: This work was supported by Instituto Politécnico de Lisboa under grant IDI&CA/IPL/2021/PLASCOGEN_ESTeSL , IDI&CA/IPL/2017/GenTox/ESTeSL, and by the Fundação para a Ciência e a Tecnologia, Portugal, under grant DSAIPA/DS/0117/2020. The human biomonitoring had financial support given by Portuguese Authority of Working Conditions (Project reference: 036APJ/09). Publisher Copyright: © 2023 The Authors
dc.description.abstractGenotoxicity is an important information that should be included in human biomonitoring programmes. However, the usually applied cytogenetic assays are laborious and time-consuming, reason why it is critical to develop rapid and economic new methods. The aim of this study was to evaluate if the molecular profile of frozen whole blood, acquired by Fourier Transform Infrared (FTIR) spectroscopy, allows to assess genotoxicity in occupational exposure to antineoplastic drugs, as obtained by the cytokinesis-block micronucleus assay. For that purpose, 92 samples of peripheral blood were studied: 46 samples from hospital professionals occupationally exposed to antineoplastic drugs and 46 samples from workers in academia without exposure (controls). It was first evaluated the metabolome from frozen whole blood by methanol precipitation of macromolecules as haemoglobin, followed by centrifugation. The metabolome molecular profile resulted in 3 ratios of spectral bands, significantly different between the exposed and non-exposed group (p < 0.01) and a spectral principal component-linear discriminant analysis (PCA-LDA) model enabling to predict genotoxicity from exposure with 73 % accuracy. After optimization of the dilution degree and solution used, it was possible to obtain a higher number of significant ratios of spectral bands, i.e., 10 ratios significantly different (p < 0.001), highlighting the high sensitivity and specificity of the method. Indeed, the PCA-LDA model, based on the molecular profile of whole blood, enabled to predict genotoxicity from the exposure with an accuracy, sensitivity, and specificity of 92 %, 93 % and 91 %, respectively. All these parameters were achieved based on 1 μL of frozen whole blood, in a high-throughput mode, i.e., based on the simultaneous analysis of 92 samples, in a simple and economic mode. In summary, it can be conclude that this method presents a very promising potential for high-dimension screening of exposure to genotoxic substances.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2355859
dc.identifier.doi10.1016/j.mrgentox.2023.503681
dc.identifier.issn1383-5718
dc.identifier.otherPURE: 89588447
dc.identifier.otherPURE UUID: 54aa4307-0425-45e2-bb06-01bdf35f93de
dc.identifier.otherScopus: 85170430854
dc.identifier.otherPubMed: 37770138
dc.identifier.otherWOS: 001076457900001
dc.identifier.urihttp://hdl.handle.net/10362/166843
dc.identifier.urlhttps://www.scopus.com/pages/publications/85170430854
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAntineoplastics
dc.subjectCytokinesis-blocked micronucleus assay
dc.subjectFrozen blood
dc.subjectFTIR-spectroscopy
dc.subjectGenotoxicity
dc.subjectMolecular profile
dc.subjectGenetics
dc.subjectHealth, Toxicology and Mutagenesis
dc.titleBlood molecular profile to predict genotoxicity from exposure to antineoplastic drugsen
dc.typejournal article
degois.publication.titleMutation Research - Genetic Toxicology and Environmental Mutagenesis
degois.publication.volume891
dspace.entity.typePublication
rcaap.rightsopenAccess

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