Rasmussen ES
Institute of Food Safety and Toxicology, Danish Veterinary and Food Administration, DK-2860 Soeborg, Denmark.
In Vitr Mol Toxicol. 1999;12(3):125-132.
The cytotoxicity of MEIC chemicals Nos. 11-30 was evaluated by determination of neutral red uptake in Balb/c 3T3 mouse fibroblasts with and without the addition of a microsomal activation mixture. The use of microsomes significantly decreased the cytotoxicity of malathion, 2,4-dichlorophenoxyacetic acid, propranolol, thioridazine, lithium sulfate, copper sulfate and thallium sulfate, whereas the cytotoxicity of 1,1,1-trichloroethylene, phenol, nicotine, and paraquat was significantly increased by use of the microsomal activation mixture. These cytotoxicity data are in line with observations in other studies on microsomal modulation of the cytotoxicity of the test substances. Moderate to good correlations were found between the cytotoxicity data and rodent lethality data, and the addition of microsomes slightly improved the in vitro/in vivo concordance. The evidence to support the relevance of the in vitro/in vivo correlations obtained in the MEIC project is limited due to a high variability on the in vivo lethality data and a large interlaboratory variation on the in vitro data.
通过测定添加和不添加微粒体活化混合物时Balb/c 3T3小鼠成纤维细胞对中性红的摄取,评估了MEIC编号11 - 30化学品的细胞毒性。微粒体的使用显著降低了马拉硫磷、2,4 - 二氯苯氧乙酸、普萘洛尔、硫利达嗪、硫酸锂、硫酸铜和硫酸铊的细胞毒性,而使用微粒体活化混合物则显著增加了1,1,1 - 三氯乙烯、苯酚、尼古丁和百草枯的细胞毒性。这些细胞毒性数据与其他关于微粒体对受试物质细胞毒性调节的研究观察结果一致。在细胞毒性数据和啮齿动物致死性数据之间发现了中度到良好的相关性,并且添加微粒体略微改善了体外/体内的一致性。由于体内致死性数据的高度变异性和体外数据的较大实验室间差异,支持MEIC项目中获得的体外/体内相关性的证据有限。