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Advisor(s)
Abstract(s)
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.
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).
Keywords
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
Citation
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.
Publisher
Elsevier