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使用人类细胞进行药理学和毒理学研究的优缺点。

Advantages and disadvantages of using human cells for pharmacological and toxicological studies.

作者信息

Hawksworth G M

机构信息

Clinical Pharmacology Unit, Department of Medicine and Therapeutics, Foresterhill, Aberdeen, UK.

出版信息

Hum Exp Toxicol. 1994 Aug;13(8):568-73. doi: 10.1177/096032719401300811.

Abstract
  1. Marked species differences in the distribution and affinity of drug receptors, and in the patterns of biotransformation and susceptibility to the toxicity of xenobiotics, provide the impetus for using human tissues for pharmacological and toxicological studies. 2. Studies with intact cells facilitate the correlation of xenobiotic metabolism with cellular indices of toxicity, which can provide the mechanistic basis for understanding species differences in toxicity. 3. Human cells in suspension or primary culture reflect the variability in susceptibility to toxicity in a population. 4. The current limitation to these studies is scarcity of human material, the need for improved (cryo)preservation techniques for human hepatocytes/precision-cut slices and difficulties in predicting in vivo exposure-risk relationships from in vitro dose-response relationships.
摘要
  1. 药物受体的分布和亲和力、生物转化模式以及对外源化合物毒性的易感性存在显著的物种差异,这为使用人体组织进行药理学和毒理学研究提供了动力。2. 对完整细胞的研究有助于将外源化合物代谢与细胞毒性指标相关联,这可为理解毒性的物种差异提供机制基础。3. 悬浮或原代培养的人体细胞反映了人群中毒性易感性的变异性。4. 这些研究目前的局限性在于人体材料稀缺、需要改进人肝细胞/精密切割切片的(低温)保存技术,以及难以从体外剂量反应关系预测体内暴露风险关系。

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