Jover R, Ponsoda X, Castell J V, Gómez-Lechón M J
Unidad de Hepatologia Experimental, Centro de Investigación, Hospital Universitario "La Fe", SVS, Avda Campanar 21, E-46009 Valencia, Spain.
Toxicol In Vitro. 1992 Jan;6(1):47-52. doi: 10.1016/0887-2333(92)90084-5.
The cytotoxic effect of the first 10 chemicals on the MEIC list (evaluated in the Multicentre Evaluation of In Vitro Cytotoxicity organized by the Scandinavian Society of Cell Toxicology) was evaluated on human and rat cultured hepatocytes and in the non-hepatic murine 3T3 cell line. The MTT test was used as an endpoint to evaluate cytotoxicity after 24 hr of exposure to the chemicals. The predictability of human toxicity using human hepatocytes was analysed and compared with the results using rodent cell culture systems and rat and mouse LD(50) tests. Ferrous sulphate, diazepam and isopropyl alcohol produced about the same toxicity in all three cell culture models; paracetamol and acetylsalicylic acid were more toxic to human and rat hepatocytes than to mouse 3T3 cells; amitriptyline, ethylene glycol, methanol and ethanol were more toxic to human hepatocytes than to rodent cells. Digoxin was the most cytotoxic chemical to human hepatocytes (IC(50), 4.9 nm), the alcoholic compounds (isopropanol, ethylene glycol, ethanol and methanol) were the least toxic (IC(50), 125-819 mm) and paracetamol, acetylsalicylic acid, ferrous sulphate, diazepam and amitriptyline showed intermediate cytotoxicities (IC(50), 0.05-6 mm). The data suggest that for these 10 chemicals, acute toxicity in humans was more accurately predicted using human hepatocytes than using rat hepatocytes or mouse non-hepatic 3T3 cells.
对MEIC清单上的前10种化学物质（在由斯堪的纳维亚细胞毒理学协会组织的体外细胞毒性多中心评估中进行评估）的细胞毒性作用，在人及大鼠培养肝细胞以及非肝性小鼠3T3细胞系中进行了评估。MTT试验用作在接触化学物质24小时后评估细胞毒性的终点。分析了使用人肝细胞预测人类毒性的可预测性，并与使用啮齿动物细胞培养系统以及大鼠和小鼠LD(50)试验的结果进行了比较。硫酸亚铁、地西泮和异丙醇在所有三种细胞培养模型中产生的毒性大致相同；对乙酰氨基酚和乙酰水杨酸对人及大鼠肝细胞的毒性比对小鼠3T3细胞的毒性更大；阿米替林、乙二醇、甲醇和乙醇对人肝细胞的毒性比对啮齿动物细胞的毒性更大。地高辛是对人肝细胞毒性最大的化学物质（IC(50)，4.9纳米），醇类化合物（异丙醇、乙二醇、乙醇和甲醇）毒性最小（IC(50)，125 - 819毫米），对乙酰氨基酚、乙酰水杨酸、硫酸亚铁、地西泮和阿米替林表现出中等细胞毒性（IC(50)，0.05 - 6毫米）。数据表明，对于这10种化学物质，使用人肝细胞比使用大鼠肝细胞或小鼠非肝3T3细胞能更准确地预测人类急性毒性。
