Barile F A, Dierickx P J, Kristen U
Department of Health Sciences, City University of New York at York College, Jamaica.
Cell Biol Toxicol. 1994 Jun;10(3):155-62. doi: 10.1007/BF00757558.
This study was designed to compare the cytotoxic concentrations of chemicals, determined with three independent in vitro cytotoxicity testing protocols, with each other and with established animal LD50 values, and against human toxic concentrations for the same chemicals. Ultimately, these comparisons allow us to evaluate the potential of in vitro cell culture methods for the ability to screen a variety of chemicals for prediction of human toxicity. Each laboratory independently tested 50 chemicals with known human lethal plasma concentrations and LD50 values. Two of the methods used monolayer cell cultures to measure the incorporation of radiolabeled amino acids into newly synthesized proteins and cellular protein content, while the third technique used the pollen tube growth test. The latter is based on the photometric quantification of pollen tube mass production in suspension culture. Experiments were performed in the absence or presence of increasing doses of the test chemical, during an 18- to 24-h incubation. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxic concentrations confirms previous independent findings that the experimental IC50 values are more accurate predictors of human toxicity than equivalent toxic blood concentrations (HETC values) derived from rodent LD50s. In addition, there were no conclusive statistical differences among the methods. It is anticipated that, together, these procedures can be used as a battery of tests to supplement or replace currently used animal protocols for human risk assessment.
本研究旨在比较通过三种独立的体外细胞毒性测试方案测定的化学物质的细胞毒性浓度，相互之间以及与既定的动物半数致死量（LD50）值进行比较，并与相同化学物质的人体毒性浓度进行比较。最终，这些比较使我们能够评估体外细胞培养方法筛选各种化学物质以预测人体毒性的潜力。每个实验室独立测试了50种已知人体致死血浆浓度和LD50值的化学物质。其中两种方法使用单层细胞培养来测量放射性标记氨基酸掺入新合成蛋白质和细胞蛋白质含量，而第三种技术使用花粉管生长试验。后者基于悬浮培养中花粉管大量产生的光度法定量。在18至24小时的孵育期间，在不存在或存在递增剂量的测试化学品的情况下进行实验。通过线性回归分析后从浓度-效应曲线推断抑制浓度。细胞毒性浓度的比较证实了先前的独立研究结果，即实验性半数抑制浓度（IC50）值比从啮齿动物LD50得出的等效毒性血液浓度（HETC值）更准确地预测人体毒性。此外，这些方法之间没有确凿的统计学差异。预计这些程序可以一起用作一组测试，以补充或取代目前用于人体风险评估的动物实验方案。
