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一种基于血清分子图谱预测遗传毒性效应的新方法。

A new method to predict genotoxic effects based on serum molecular profile.

作者信息

Araújo Rúben, Ramalhete Luís, Paz Hélder, Ladeira Carina, Calado Cecília R C

机构信息

ISEL - Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, Rua Conselheiro Emídio Navarro 1, 1959-007 Lisboa, Portugal.

ISEL - Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, Rua Conselheiro Emídio Navarro 1, 1959-007 Lisboa, Portugal; CSTL-T - Centro de Sangue e da Transplantação de Lisboa - Instituto Português do Sangue e Transplantação, IP, Alameda das Linhas de Torres, n°117, 1769-001 Lisboa, Portugal.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Jul 5;255:119680. doi: 10.1016/j.saa.2021.119680. Epub 2021 Mar 8.

DOI:10.1016/j.saa.2021.119680
PMID:33744838
Abstract

It is critical to develop new methods to assess genotoxic effects in human biomonitoring since the conventional methods are usually laborious, time-consuming, and expensive. It is aimed to evaluate if the analysis of a drop of serum by Fourier Transform Infrared spectroscopy, allow to assess genotoxic effects in occupational exposure to cytostatic drugs in hospital professionals, as obtained by the lymphocyte cytokinesis-block micronucleus assay. It was considered peripheral blood from hospital professionals exposed to cytostatic drugs (n = 22) and from a non-exposed group (n = 36). It was observed that workers occupationally exposed presented a higher number of micronuclei (p < 0.05) in lymphocytes, in relation to the non-exposed group. The serum Fourier Transform Infrared spectra from exposed workers presented diverse different peaks (p < 0.01) in relation to the non-exposed group. The hierarchical cluster analysis of serum spectra separated serum samples of the exposed group from the non-exposed group with 61% sensitivity and 88% specificity. A support vector machine model of serum spectra enables to predict exposure with high accuracy (0.91), precision (0.89), sensitivity (0.86), F1 score (0.87) and AUC (0.96). Therefore, Fourier Transform Infrared spectroscopic analysis of a drop of serum enabled to predict in a rapid and simple mode the genotoxic effects of cytostatic drugs. The method presents therefore potential for high-dimension screening of exposure of genotoxic substances, due to its simplicity and rapid setup mode.

摘要

开发新的方法来评估人体生物监测中的遗传毒性效应至关重要,因为传统方法通常费力、耗时且昂贵。本研究旨在评估通过傅里叶变换红外光谱分析一滴血清,是否能够像淋巴细胞胞质分裂阻断微核试验那样评估医院专业人员职业接触细胞毒性药物时的遗传毒性效应。研究纳入了接触细胞毒性药物的医院专业人员(n = 22)和未接触组(n = 36)的外周血。结果发现,与未接触组相比,职业接触的工人淋巴细胞中的微核数量更多(p < 0.05)。与未接触组相比,接触工人的血清傅里叶变换红外光谱呈现出不同的峰(p < 0.01)。血清光谱的层次聚类分析将接触组和未接触组的血清样本分开,灵敏度为61%,特异性为88%。血清光谱的支持向量机模型能够以高精度(0.91)、精确率(0.89)、灵敏度(0.86)、F1分数(0.87)和AUC(0.96)预测接触情况。因此,一滴血清的傅里叶变换红外光谱分析能够快速、简单地预测细胞毒性药物的遗传毒性效应。由于其简单性和快速设置模式,该方法具有对遗传毒性物质接触进行高维筛选的潜力。

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引用本文的文献

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Arch Toxicol. 2023 Jun;97(6):1453-1517. doi: 10.1007/s00204-023-03481-9. Epub 2023 Apr 26.