ToxCast Cytotoxicity-Associated Burst

Title: ToxCast Cytotoxicity-Associated Burst Paragraph: Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Evaluating the ToxCast high-throughput screening library, many chemicals show activation of large numbers of assays over a narrow range of concentrations in which cell stress and cytotoxicity are also seen. We term this phenomenon the cytotoxicity-associated “burst”. Whereas some of the assay activity in this concentration range may represent chemical effects on the intended target of the assay, some of it is not. In such situations, activity represents a false positive response that can be ascribed to assay interference processes. This phenomenon raises the need to establish a concentration threshold at which each chemical begins to drive activity across multiple and diverse cell stress and cytotoxicity assays by initiating this cytotoxicity-associated burst of activity. Judson R, et al . Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space. Toxicol Sci. 2016 Oct;153(2):409. doi: 10.1093/toxsci/kfw148. Epub 2016 Sep 7. Erratum for: Toxicol Sci. 2016 Aug;152(2):323-39. PMID: 27605417; PMCID: PMC7297301. <br> These data are based on ToxCast invitroDBv3.5标题：ToxCast细胞毒性相关爆发（Cytotoxicity-Associated Burst） 段落：化学物毒性可源于特定生物分子功能的紊乱，亦可通过更为广泛的细胞应激及细胞毒性介导的过程产生。针对ToxCast高通量筛选文库开展评估时，可观察到诸多化学物在较窄浓度区间内即可激活大量检测项目，且该浓度区间同时伴随细胞应激与细胞毒性的出现。我们将该现象命名为细胞毒性相关“爆发（Cytotoxicity-Associated Burst）”。尽管该浓度区间内的部分检测活性可反映化学物对检测预期靶标的作用，但另有部分活性并非源于此类特异性作用。在此类情形下，此类活性属于假阳性响应，可归因于检测干扰过程。该现象提示，亟需确立一个浓度阈值，用于界定每种化学物通过触发此种细胞毒性相关活性爆发，从而在多种不同的细胞应激与细胞毒性检测中引发活性的起始节点。Judson R等人。《跨多样化学物与检测空间的细胞应激及细胞毒性对体外检测活性的影响分析》。《Toxicol Sci》，2016年10月；153(2):409。DOI: 10.1093/toxsci/kfw148。2016年9月7日在线发表。勘误信息见于：《Toxicol Sci》，2016年8月；152(2):323-39。PMID: 27605417；PMCID: PMC7297301。<br> 本数据集基于ToxCast体外数据库v3.5（invitroDBv3.5）