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The Use of Human Lymphocytes for the In Vitro Estimation of Acute Toxicity of Ten Chemicals from the MEIC List
Alternatives to Laboratory Animals ( IF 2.4 ) Pub Date : 1991-04-01 , DOI: 10.1177/026119299101900206
Mette Tingleff Skaanild 1 , Jørgen Clausen 1
Affiliation  

The acute cytotoxicity of ten chemicals included in the MEIC (multicentre evaluation of in vitro cytotoxicity) list has already been estimated in various cell lines, e.g. primary rat hepatocytes, HeLa cells, human hepatoma cells, and 3T3 and mouse fibroma cells. In the present study, primary cultures of human lymphocytes, with or without an S9-mix (microsomes), were used to assay for in vitro toxicity. The cultured cells were initially treated with different concentrations of the respective drugs for 24 hours. Then cellular enzymatic activity was estimated using two assay systems, namely, measurement of cytosolic LDH activity and the mitochondrial (diaphorase) MTT test. Since the biological significance of the assay of LC50 values is dependent upon the slope of the dose-response curves, the results are expressed as LC20, LC50 and LC80 values in μM for the ten drugs. A Spearman rank correlation analysis revealed a significant correlation between the results from the two assays in both cell culture systems (r=1.00 and r=0.99). The LC50 values found in the lymphocyte cultures, both with and without an S9-mix, correlated well with the results previously found using primary cultures of hepatocytes and HeLa cells.

中文翻译:

使用人类淋巴细胞对 MEIC 清单中十种化学品的急性毒性进行体外评估

MEIC(体外细胞毒性多中心评估)列表中包含的十种化学物质的急性细胞毒性已经在各种细胞系中进行了评估,例如原代大鼠肝细胞、HeLa 细胞、人肝癌细胞以及 3T3 和小鼠纤维瘤细胞。在本研究中,人类淋巴细胞的原代培养物,无论是否含有 S9 混合物(微粒体),都用于测定体外毒性。培养的细胞最初用不同浓度的相应药物处理24小时。然后使用两种测定系统评估细胞酶活性,即细胞溶质 LDH 活性的测量和线粒体(心肌黄酶)MTT 测试。由于 LC50 值测定的生物学意义取决于剂量反应曲线的斜率,因此结果表示为 LC20,十种药物的 LC50 和 LC80 值(以 μM 为单位)。Spearman 等级相关性分析揭示了两种细胞培养系统中两种测定的结果之间存在显着相关性(r=1.00 和 r=0.99)。在有和没有 S9 混合物的淋巴细胞培养物中发现的 LC50 值与先前使用肝细胞和 HeLa 细胞的原代培养物发现的结果很好地相关。
更新日期:1991-04-01
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