多层角质细胞培养用于体外毒理学研究。

Molecular toxicology Pub Date : 1987-09-01
A Hoh, K Maier, R M Dreher
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引用次数: 0

摘要

人角质形成细胞是评价皮肤细胞毒性机制和化学试剂药理学最合适的靶细胞。在与增殖的基底细胞和分化的细胞层形成融合的层状上皮后,酶解分离后的人角化细胞被收获为稳定的三维细胞聚集体,或在微滴板上用作贴壁多层,以研究不同有毒化合物的局部细胞毒性。这种测试的优点是,它使用了足够的靶细胞,并评估了测试化学物质穿透几层细胞的能力以及干扰细胞功能的能力。终点是细胞活力和细胞代谢,分别由中性红摄取和MTT减少决定。对于本研究中评估的13种化学物质,我们发现角化细胞NR 50值的效力排名与体内刺激数据之间存在良好的相关性(r = .819)。根据3T3试验和角质细胞试验的中点毒性对这些化学物质的排序也有很好的一致性(r = .945)。该试验系统在现阶段可能是对现有试验电池的补充,将取代Draize试验等体内刺激试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multilayered keratinocyte culture used for in vitro toxicology.

Human keratinocytes are the most appropriate target cells for evaluating mechanisms of skin cytotoxicity and pharmacology of chemical agents. After having formed a confluent stratified epithelium with proliferating basal cells and differentiated cell layers, human keratinocytes were harvested after enzymatic detachment as stable, three-dimensional cell aggregates or used as adherent multilayers in microtiter plates to study the local cytotoxicity of different toxic compounds. The advantage of this test is that it uses the adequate target cells and that it evaluates both the ability of the test chemical to penetrate several cellular layers as well as the ability to interfere with cellular function. The end points are cell viability and cell metabolism, which are determined by neutral red uptake and MTT reduction, respectively. For the 13 chemicals evaluated in this study we found good correlation (r = .819) between the potency rankings of keratinocyte NR 50 values and in vivo irritancy data. There was also good agreement (r = .945) between ranking of these chemicals according to midpoint toxicity of both the 3T3 assay and the keratinocyte assay. This test system might be at the present stage a supplementation of the current test battery, which shall replace in vivo irritation tests like the Draize test.

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