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体外毒理学:一项商业提议?

In vitro toxicology: a commercial proposition?

作者信息

Flint O P

机构信息

Imperial Chemical Industries PLC, Pharmaceutical Division, Macclesfield, Cheshire, UK.

出版信息

Xenobiotica. 1988 Jun;18(6):707-14. doi: 10.3109/00498258809041709.

DOI:10.3109/00498258809041709
PMID:3420946
Abstract
  1. The commercial value of any test system must be equated with its scientific value. In vitro toxicity tests only have scientific value when they are accurate models of toxicity in vivo. 2. Toxicity is a complex event so that the simple tests of cell viability are unlikely to be useful models as these tests often use cell lines which are functionally remote from cells in tissues of the whole animal. 3. Primary cultures retain their differentiated function for hours (hepatocytes) or days (nerve cells) and may acquire differentiated functions in vitro (embryo cells) and are the models of choice for predicting toxic hazard. 4. When the in vitro test is a satisfactory predictive model of toxicity there are sound commercial reasons for its use. It saves time and effort and can be used at an early stage in compound development to sort out the toxic from the non-toxic candidate compounds. Large numbers of structurally similar compounds can be tested (QSAR studies) and a greater understanding of the mechanism of toxic action can often be achieved than in vivo because of the numbers of animals required and the interplay of different organ systems in the toxic events that make interpretation difficult. Thus the in vitro test can not only save animals but can also save compounds.
摘要
  1. 任何测试系统的商业价值都必须与其科学价值等同。体外毒性试验只有在准确模拟体内毒性时才具有科学价值。2. 毒性是一个复杂的过程,因此简单的细胞活力测试不太可能成为有用的模型,因为这些测试通常使用的细胞系在功能上与整个动物组织中的细胞相差甚远。3. 原代培养物能在数小时(肝细胞)或数天(神经细胞)内保持其分化功能,并且可能在体外获得分化功能(胚胎细胞),是预测毒性危害的首选模型。4. 当体外试验是一个令人满意的毒性预测模型时,使用它有合理的商业理由。它节省时间和精力,可在化合物开发的早期用于区分有毒和无毒的候选化合物。可以测试大量结构相似的化合物(定量构效关系研究),而且由于体内试验所需的动物数量以及毒性事件中不同器官系统之间的相互作用使得解释困难,相比体内试验,体外试验往往能更深入地了解毒性作用机制。因此,体外试验不仅可以节省动物,还可以节省化合物。

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