Acute cytotoxicity testing with cultured human lung and dermal cells
Acute cytotoxicity testing with cultured human lung and dermal cells
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DOI：
10.1007/s11626-996-0011-0
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发表时间：
1998-09-01
影响因子：
2.1
通讯作者：
Cardona, M
中科院分区：
文献类型：
--
作者：
Barile, FA;Cardona, M
用培养细胞进行了广泛的体外研究，以验证基础细胞毒性理论。这一理论表明，大多数化学损伤，至少在体外，是一种或多种对哺乳动物常见的基本细胞结构和功能的损害的表现。这解释了多实验室研究结果的相似性。在培养中研究了人胎儿肺成纤维细胞（HFL1）和人皮肤成纤维细胞（WS1, Detroit551），以评估它们筛选细胞毒性的潜力。在没有或存在浓度增加的试验化学品的情况下，将融合的单层培养24小时，并使用MTT法评估毒性。线性回归分析后，根据浓度-效应曲线推断抑菌浓度。对每种细胞系的29种化学物质进行了测试，并将细胞毒性数据与啮齿动物和人类的致死浓度进行了比较。数据表明，实验IC50值与来自啮齿动物LD(50)s的等效毒性血液浓度一样准确地预测了人类毒性。此外，肺和皮肤成纤维细胞在三种细胞系之间没有显着差异。这些结果支持了人类有限细胞系具有筛选人类毒性化学物质的潜力的结论。结合先前发表的报告，这些数据表明，基础细胞毒性现象可能解释了不同人类细胞系之间结果的相似性。
An extensive in vitro study with cultured cells was conducted to test the basal cytotoxicity theory. This theory suggests that most chemical injury, at least in vitro, is a manifestation of one or more insults to the basic cellular structures and functions common to mammalian sells. This accounts for the similarity of results in multilaboratory studies. Human fetal lung fibroblasts (HFL1), and human skin fibroblasts (WS1, Detroit551) were studied in culture to evaluate their potential to screen for cytotoxicity. Confluent monolayers were incubated in the absence or presence of increasing concentrations of test chemicals for 24 h, and the MTT assay was used to assess toxicity. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Twenty-nine chemicals were tested with each cell line and the cytotoxicity data compared to rodent and human lethal concentrations. The data suggest that the experimental IC50 values are as accurate predictors of human toxicity as equivalent toxic blood concentrations derived from rodent LD(50)s. In addition, lung and skin fibroblasts revealed no significant differences among the three cell lines. The results support the conclusion that finite cell lines of human origin have the potential for screening chemicals for human toxicity. In combination with previously published reports, the data suggest that a basal cytotoxic phenomenon may explain the similarity of results among different human cell lines.