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哺乳动物细胞培养中毒性化合物的筛选。

Screening of toxic compounds in mammalian cell cultures.

作者信息

Ekwall B

出版信息

Ann N Y Acad Sci. 1983;407:64-77. doi: 10.1111/j.1749-6632.1983.tb47814.x.

DOI:10.1111/j.1749-6632.1983.tb47814.x
PMID:6349488
Abstract

The cytotoxic concentrations of about 100 randomly selected drugs and chemicals, tested on HeLa cells in the MIT-24 system and/or in primary cultures of fetal chicken cells, were compared with the lethal doses and/or concentrations of the agents in the mouse and in man. Most agents (80%) had a similar toxicity in vitro and in vivo, suggesting a lethal interference in man with basal functions common to all specialized human tissues as well as cultured cells, i.e., basal cytotoxicity. This high frequency of basally cytotoxic agents opens possibilities for screening chemicals for toxicity and for studying cytotoxic mechanisms with a standard battery of a few appropriate cell tests. This battery may be used in three ways: (1) to study cytotoxic mechanisms of all chemicals, and apply the resulting knowledge to understanding toxicity in man of basally cytotoxic agents; (2) to supplement conventional animal tests in acute toxicity test programs; (3) to screen chemicals and extracts for their potential basal cytotoxicity. To validate these ideas and to select suitable tests for the battery, results from cytotoxicity tests on a wide variety of chemicals in several in vitro systems must be compared with one another and with the toxicity of the agents in animals and man.

摘要

在MIT - 24系统中对HeLa细胞和/或在鸡胚细胞原代培养物中测试了约100种随机选择的药物和化学物质的细胞毒性浓度,并将其与这些药剂在小鼠和人体中的致死剂量和/或浓度进行了比较。大多数药剂(80%)在体外和体内具有相似的毒性,这表明其对人体所有特殊组织以及培养细胞共有的基础功能具有致死性干扰,即基础细胞毒性。这种具有基础细胞毒性的药剂的高频率出现为筛选化学物质的毒性以及用一些合适的细胞测试标准组合来研究细胞毒性机制提供了可能性。该测试组合可用于三种方式:(1)研究所有化学物质的细胞毒性机制,并将所得知识应用于理解具有基础细胞毒性的药剂对人体的毒性;(2)在急性毒性测试程序中补充传统的动物测试;(3)筛选化学物质和提取物的潜在基础细胞毒性。为了验证这些想法并为测试组合选择合适的测试,必须将几种体外系统中对多种化学物质的细胞毒性测试结果相互比较,并与这些药剂在动物和人体中的毒性进行比较。

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