Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs

Detalhes bibliográficos
Autor(a) principal: Ladeira, Carina
Data de Publicação: 2023
Outros Autores: Araújo, Rúben, Ramalhete, Luís, Teixeira, Hélder, Calado, Cecília R. C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.21/16384
Resumo: 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 the Portuguese Authority of Working Conditions (Project reference: 036APJ/09).
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spelling Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugsMolecular profileFTIR-spectroscopyGenotoxicityCytokinesis-blocked micronucleus assayFrozen bloodAntineoplasticsIDI&CA/IPL/2021/PLASCOGEN_ESTeSLIDI&CA/IPL/2017/GenTox/ESTeSLFCT_DSAIPA/DS/0117/2020ACT_036APJ/09This 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).Genotoxicity 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.ElsevierRCIPLLadeira, CarinaAraújo, RúbenRamalhete, LuísTeixeira, HélderCalado, Cecília R. C.2023-08-22T12:02:41Z2023-102023-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/16384engLadeira 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;891:503681.10.1016/j.mrgentox.2023.503681info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-11T02:15:32Zoai:repositorio.ipl.pt:10400.21/16384Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:27:24.559236Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
title Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
spellingShingle Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
Ladeira, Carina
Molecular profile
FTIR-spectroscopy
Genotoxicity
Cytokinesis-blocked micronucleus assay
Frozen blood
Antineoplastics
IDI&CA/IPL/2021/PLASCOGEN_ESTeSL
IDI&CA/IPL/2017/GenTox/ESTeSL
FCT_DSAIPA/DS/0117/2020
ACT_036APJ/09
title_short Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
title_full Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
title_fullStr Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
title_full_unstemmed Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
title_sort Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs
author Ladeira, Carina
author_facet Ladeira, Carina
Araújo, Rúben
Ramalhete, Luís
Teixeira, Hélder
Calado, Cecília R. C.
author_role author
author2 Araújo, Rúben
Ramalhete, Luís
Teixeira, Hélder
Calado, Cecília R. C.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv RCIPL
dc.contributor.author.fl_str_mv Ladeira, Carina
Araújo, Rúben
Ramalhete, Luís
Teixeira, Hélder
Calado, Cecília R. C.
dc.subject.por.fl_str_mv Molecular profile
FTIR-spectroscopy
Genotoxicity
Cytokinesis-blocked micronucleus assay
Frozen blood
Antineoplastics
IDI&CA/IPL/2021/PLASCOGEN_ESTeSL
IDI&CA/IPL/2017/GenTox/ESTeSL
FCT_DSAIPA/DS/0117/2020
ACT_036APJ/09
topic Molecular profile
FTIR-spectroscopy
Genotoxicity
Cytokinesis-blocked micronucleus assay
Frozen blood
Antineoplastics
IDI&CA/IPL/2021/PLASCOGEN_ESTeSL
IDI&CA/IPL/2017/GenTox/ESTeSL
FCT_DSAIPA/DS/0117/2020
ACT_036APJ/09
description 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 the Portuguese Authority of Working Conditions (Project reference: 036APJ/09).
publishDate 2023
dc.date.none.fl_str_mv 2023-08-22T12:02:41Z
2023-10
2023-10-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.21/16384
url http://hdl.handle.net/10400.21/16384
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Ladeira 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.
10.1016/j.mrgentox.2023.503681
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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