Smith L L, Lewis C P, Wyatt I, Cohen G M
ICI Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Environ Health Perspect. 1990 Apr;85:25-30. doi: 10.1289/ehp.85-1568342.
The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization of the process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell. With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells. In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system.
与其他组织相比，除草剂百草枯在体内和体外都被肺选择性积累，这一发现为其对肺的选择性毒性提供了解释。这种摄取过程依赖能量并遵循饱和动力学。对该过程的表征导致鉴定出作为该系统天然底物的内源性化学物质。其中包括一系列二胺和多胺，以及二氨基二硫化物胱胺。似乎百草枯由于与这些内源性多胺具有特定的结构相似性，而被肺错误地积累。这种摄取过程特定地位于肺泡II型细胞、克拉拉细胞，可能还有肺泡I型细胞中。随着对该系统积累化学物质的结构要求的认识不断发展，有可能预测哪些化学物质会被肺积累，或者设计靶向肺泡上皮细胞和克拉拉细胞的分子。从更广泛的角度来看，在许多癌细胞或组织中都发现了这种多胺摄取系统。有了对肺摄取系统的了解，应该有可能设计出能特异性集中在具有该系统的细胞中的药物。
