Baron J, Voigt J M
Department of Pharmacology, University of Iowa, Iowa City 52242.
Pharmacol Ther. 1990;47(3):419-45. doi: 10.1016/0163-7258(90)90065-a.
The metabolism of xenobiotics within lung often leads to toxicity, although certain pulmonary cells are more readily damaged than others. This differential susceptibility can result from cell-specific differences in xenobiotic activation and detoxication. The localization and distribution of xenobiotic-metabolizing enzymes (cytochromes P-450, NADPH-cytochrome P-450 reductase, epoxide hydrolase, glutathione S-transferases, UDP-glucuronosyltransferases, and a sulfotransferase) and of aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity determined immunohistochemically and histochemically, respectively, within lung are discussed. Findings reveal that xenobiotics can be metabolized in situ, albeit to different extents, by bronchial epithelial cells, Clara and ciliated bronchiolar epithelial cells, and type II pneumocytes and other alveolar wall cells and that enzymes and activities are not necessarily induced uniformly among these cells.
外源性物质在肺内的代谢通常会导致毒性，尽管某些肺细胞比其他细胞更容易受损。这种易感性差异可能源于外源性物质激活和解毒过程中的细胞特异性差异。本文讨论了通过免疫组织化学和组织化学方法分别测定的外源性物质代谢酶（细胞色素P-450、NADPH-细胞色素P-450还原酶、环氧化物水解酶、谷胱甘肽S-转移酶、UDP-葡萄糖醛酸基转移酶和一种磺基转移酶）以及芳烃（苯并[a]芘）羟化酶活性在肺内的定位和分布。研究结果表明，支气管上皮细胞、克拉拉细胞和纤毛细支气管上皮细胞、II型肺泡上皮细胞及其他肺泡壁细胞能够在原位对外源性物质进行代谢，尽管程度不同，而且这些细胞中的酶和活性不一定会被均匀诱导。
