Skin toxicity and cellular metabolism: in vitro models
Skin toxicity and cellular metabolism: in vitro models
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皮肤毒性和细胞代谢：体外模型
DOI：
10.1111/j.1365-2133.1986.tb02119.x
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发表时间：
1986
影响因子：
10.3
通讯作者：
U. Reichert
中科院分区：
文献类型：
--
作者：
U. Reichert
培养的人类细胞越来越多地被用作体外模型来研究药物诱导毒性的机制。在特定药物的影响下，通过测量细胞脱离、细胞内物质（ATP、蛋白质、DNA）的释放、排除台锥虫蓝或重要染料的摄取、胸腺嘧啶掺入和蛋白质生物合成的抑制等，监测了细胞特性的变化，如锚定依赖性细胞对其培养载体的粘附性、细胞膜渗透性、增殖、呼吸和总体代谢活性。以及气体交换和产热的变化。为了评估这种方法在皮肤药理学和毒理学上的适用性，我们研究了三种不同类型的抗银屑病药物（蒽醌、8-甲氧基补骨脂素联合UVA、类维生素a）对培养的人真皮成纤维细胞和/或转化的表皮角质形成细胞的治疗效果。已知这些药物具有一定的皮肤毒性作用，如刺激、瘙痒或皮肤干燥。本综述讨论了使用细胞培养模型来研究皮肤毒性化合物的作用方式，将炭疽病和PUVA的抗银屑病活性与其细胞毒性潜能联系起来，并讨论了在何种程度上和在何种条件下，体外结果可以推断到体内情况的问题。
Human cells in culture are being used with increasing frequency as m vitro models for studying the mechanisms of drug-induced toxicity. Changes in cellular properties such as the adhesiveness of anchorage-dependent cells to their culture support, cell membrane permeability, proliferation, respiration and overall metabolic activity, have been monitored under the influence of a given drug by measuring, for example, cell detachment, release of intracellular material (ATP, proteins, DNA), exclusion of trypan blue or uptake of vital dyes, inhibition of thymidine incorporation and protein biosynthesis, as well as alterations in gas exchange and heat production. In order to evaluate the applicability of this approach to skin pharmacology and toxicology, we have studied the effects of treatment with three different classes of antipsoriatic drugs (anthralin, 8-methoxypsoralen in combination with UVA, retinoids) on cultured human dermal fibroblasts and/or transformed epidermal keratinocytes. These drugs are known to exert certain dermatotoxic effects such as irritation, pruritus or skin dryness. The present review of these studies discusses the use of cell culture models for investigating the mode of action of dermatotoxic compounds, relates the antipsoriatic activity of anthralin and PUVA to their cytotoxic potential, and deals with the problem ofthe extent to which, and under which conditions, in vitro results can be extrapolated to the situation in vivo.