Cingi M R, De Angelis I, Fortunati E, Reggiani D, Bianchi V, Tiozzo R, Zucco F
Institute of General Pathology, University of Modena, Italy.
Toxicol In Vitro. 1991;5(2):119-25. doi: 10.1016/0887-2333(91)90031-8.
A major problem that interferes with the introduction of in vitro tests for toxicological risk assessment is that of defining reliable standardized protocols. This issue was approached in the present study with an interlaboratory comparison of three cytotoxicity assays detecting chemical toxicity as impairment of cell viability in confluent cultures, reduction of colony forming ability, and inhibition of cell proliferation over 3 days of treatment. The study was performed using V79 cells, which are unable to activate indirectly-acting xenobiotics, and six chemicals with different mechanisms of action: two antioxidants (butylated hydroxyanisole and butylated hydroxytoluene), an inhibitor of protein synthesis (cycloheximide), an alkylating agent requiring metabolic activation (cyclophosphamide), an uncoupler of oxidative phosphorylation (dinitrophenol), and a genotoxic metal salt (potassium dichromate). The three tests produced the same rank of relative toxic potency for the tested chemicals, based on LC(50) values. The cell viability test appeared to be the most suited for the screening of unknown chemicals, given its simplicity and better reproducibility.
妨碍引入用于毒理学风险评估的体外试验的一个主要问题是定义可靠的标准化方案。在本研究中，通过对三种细胞毒性试验进行实验室间比较来探讨这个问题，这三种试验检测化学物质毒性的方式分别为：检测汇合培养物中细胞活力的损伤、集落形成能力的降低以及在3天处理期内细胞增殖的抑制。该研究使用了无法激活间接作用外源性物质的V79细胞，以及六种具有不同作用机制的化学物质：两种抗氧化剂（丁基羟基茴香醚和丁基羟基甲苯）、一种蛋白质合成抑制剂（环己酰亚胺）、一种需要代谢激活的烷化剂（环磷酰胺）、一种氧化磷酸化解偶联剂（二硝基苯酚）和一种遗传毒性金属盐（重铬酸钾）。基于半数致死浓度（LC50）值，这三种试验对所测试化学物质产生了相同的相对毒性效力排名。鉴于细胞活力试验的简单性和更好的可重复性，它似乎最适合用于筛选未知化学物质。
