Barile F A, Cardona M
Department of Health Sciences, City University of New York at York College, Jamaica 11451, USA.
In Vitro Cell Dev Biol Anim. 1998 Sep;34(8):631-5. doi: 10.1007/s11626-996-0011-0.
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 cells. 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 LD50s. 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.
进行了一项广泛的针对培养细胞的体外研究，以检验基础细胞毒性理论。该理论表明，大多数化学损伤，至少在体外，是对哺乳动物细胞共有的基本细胞结构和功能的一种或多种损害的表现。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、底特律551），以评估它们筛选细胞毒性的潜力。将汇合的单层细胞在不存在或存在浓度递增的测试化学品的情况下孵育24小时，并使用MTT法评估毒性。通过线性回归分析后从浓度-效应曲线外推抑制浓度。用每种细胞系测试了29种化学品，并将细胞毒性数据与啮齿动物和人类的致死浓度进行比较。数据表明，实验IC50值作为人类毒性的预测指标与从啮齿动物LD50得出的等效毒性血药浓度一样准确。此外，肺成纤维细胞和皮肤成纤维细胞在这三种细胞系之间没有显示出显著差异。结果支持这样的结论，即有限的人源细胞系有筛选化学品对人类毒性的潜力。结合先前发表的报告，数据表明基础细胞毒性现象可能解释了不同人类细胞系结果的相似性。
