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Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs

2023-10Journal article Open access
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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.date.accessioned2023-08-22T12:02:41Z
dc.date.available2023-08-22T12:02:41Z
dc.date.issued2023-10
dc.descriptionThis 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 the Portuguese Authority of Working Conditions (Project reference: 036APJ/09).pt_PT
dc.description.abstractGenotoxicity is important information that should be included in human biomonitoring programs. However, the usually applied cytogenetic assays are laborious and time-consuming, the reason why it is critical to developing 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 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 concluded that this method presents a very promising potential for high-dimension screening of exposure to genotoxic substances.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLadeira C, Araújo R, Ramalhete L, Teixeira H, Calado CR. Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs. Mutat Res Genet Toxicol Environ Mutagen. 2023;891:503681.pt_PT
dc.identifier.doi10.1016/j.mrgentox.2023.503681pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/16384
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationIDI&CA/IPL/2021/PLASCOGEN_ESTeSLpt_PT
dc.relationIDI&CA/IPL/2017/GenTox/ESTeSLpt_PT
dc.relationACT_036APJ/09pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1383571823000992pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectMolecular profilept_PT
dc.subjectFTIR-spectroscopypt_PT
dc.subjectGenotoxicitypt_PT
dc.subjectCytokinesis-blocked micronucleus assaypt_PT
dc.subjectFrozen bloodpt_PT
dc.subjectAntineoplasticspt_PT
dc.subjectIDI&CA/IPL/2021/PLASCOGEN_ESTeSLpt_PT
dc.subjectIDI&CA/IPL/2017/GenTox/ESTeSLpt_PT
dc.subjectFCT_DSAIPA/DS/0117/2020pt_PT
dc.subjectACT_036APJ/09pt_PT
dc.titleBlood molecular profile to predict genotoxicity from exposure to antineoplastic drugspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/DSAIPA%2FDS%2F0117%2F2020/PT
oaire.citation.startPage503681pt_PT
oaire.citation.titleMutation Research/Genetic Toxicology and Environmental Mutagenesispt_PT
oaire.citation.volume891pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameLadeira
person.givenNameCarina
person.identifier144237
person.identifier.ciencia-id801C-1BBA-1D9E
person.identifier.orcid0000-0001-5588-0074
person.identifier.ridJ-2572-2012
person.identifier.scopus-author-id36463788000
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication1aef4b60-4197-436b-84ab-80d31cbaed33
relation.isAuthorOfPublication.latestForDiscovery1aef4b60-4197-436b-84ab-80d31cbaed33
relation.isProjectOfPublication8f80f51c-b563-49e2-9864-a2c78479fc19
relation.isProjectOfPublication.latestForDiscovery8f80f51c-b563-49e2-9864-a2c78479fc19

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