Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing.

Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing.
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刮痕负载-染料转移试验在非遗传毒性致癌物检测中的适用性

DOI:
10.3390/ijms22168977
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发表时间:
2021-08-20
影响因子:
5.6
通讯作者:
Babica P
Babica P
中科院分区:
生物学2区
文献类型:
--
作者:
Sovadinová I;Upham BL;Trosko JE;Babica P

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缝隙连接细胞间通讯失调(GJIC)被认为是鉴定非遗传毒性致癌物(NGTxC)的关键标志之一。目前,存在针对缝隙连接标志的体外分析的需求,这将有可能最终成为NGTxC测试和评估(IATA)综合方法的组成部分。刮擦负载-染料转移(SL-DT)技术是一种在多种体外培养的哺乳动物细胞中评价GJIC功能的简单方法,是一种有趣的候选方法。在评价GJIC的各种技术中,SL-DT法在毒理学和肿瘤促进研究中经常被用来评价各种化学物质对GJIC的影响。在这篇综述中,我们系统地检索了现有的文献,以收集在大鼠肝上皮细胞系WB-F344中使用SL-DT法评估GJIC的文献,这些化学物质特别是环境和食物毒物、药物、生殖、心脏和神经毒物以及化学肿瘤促进剂处理后。我们结合已知的被评估化学物质的促癌活性和致癌性,讨论了SL-DT试验得出的结果,以评估SL-DT试验在识别致癌物方面的敏感性、特异性和准确性的预测能力。这些数据代表了关于SL-DT试验在IATA框架内测试NGTxC的适用性的重要信息。
Dysregulation of gap junction intercellular communication (GJIC) is recognized as one of the key hallmarks for identifying non-genotoxic carcinogens (NGTxC). Currently, there is a demand for in vitro assays addressing the gap junction hallmark, which would have the potential to eventually become an integral part of an integrated approach to the testing and assessment (IATA) of NGTxC. The scrape loading-dye transfer (SL-DT) technique is a simple assay for the functional evaluation of GJIC in various in vitro cultured mammalian cells and represents an interesting candidate assay. Out of the various techniques for evaluating GJIC, the SL-DT assay has been used frequently to assess the effects of various chemicals on GJIC in toxicological and tumor promotion research. In this review, we systematically searched the existing literature to gather papers assessing GJIC using the SL-DT assay in a rat liver epithelial cell line, WB-F344, after treating with chemicals, especially environmental and food toxicants, drugs, reproductive-, cardio- and neuro-toxicants and chemical tumor promoters. We discuss findings derived from the SL-DT assay with the known knowledge about the tumor-promoting activity and carcinogenicity of the assessed chemicals to evaluate the predictive capacity of the SL-DT assay in terms of its sensitivity, specificity and accuracy for identifying carcinogens. These data represent important information with respect to the applicability of the SL-DT assay for the testing of NGTxC within the IATA framework.
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