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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.
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Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.

机译:通过分析人类THP-1单核细胞的基因表达变化来预测化学物质的接触致敏性。

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摘要

The aim of this study was to find differentially regulated genes in THP-1 monocytic cells exposed to sensitizers and nonsensitizers and to investigate if such genes could be reliable markers for an in vitro predictive method for the identification of skin sensitizing chemicals. Changes in expression of 35 genes in the THP-1 cell line following treatment with chemicals of different sensitizing potential (from nonsensitizers to extreme sensitizers) were assessed using real-time PCR. Verification of 13 candidate genes by testing a large number of chemicals (an additional 22 sensitizers and 8 nonsensitizers) revealed that prediction of contact sensitization potential was possible based on evaluation of changes in three genes: IL8, HMOX1 and PAIMP1. In total, changes in expression of these genes allowed correct detection of sensitization potential of 21 out of 27 (78%) test sensitizers. The gene expression levels inside potency groups varied and did not allow estimation of sensitization potency of test chemicals. Results of this study indicate that evaluation of changes in expression of proposed biomarkers in THP-1 cells could be a valuable model for preliminary screening of chemicals to discriminate an appreciable majority of sensitizers from nonsensitizers.
机译:这项研究的目的是在暴露于敏化剂和非敏化剂的THP-1单核细胞中找到差异调节的基因,并研究这些基因是否可以作为鉴定皮肤敏化化学品的体外预测方法的可靠标记。使用实时PCR评估了在THP-1细胞系中35种基因的表达变化后,使用了不同敏化潜能的化学品(从非敏化剂到极敏化剂)。通过测试大量的化学物质(另外22种敏化剂和8种非敏化剂)验证了13个候选基因,发现基于对三个基因IL8,HMOX1和PAIMP1的变化进行评估,可以预测接触致敏电位。总体而言,这些基因表达的变化允许正确检测27种(78%)测试敏化剂中的21种敏化潜能。效力组内部的基因表达水平各不相同,因此无法估算受试化学品的致敏效力。这项研究的结果表明,评估THP-1细胞中拟议生物标志物表达的变化可能是有价值的模型,可用于初步筛选化学物质以区分相当大的敏化剂和非敏化剂。

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