Skelly M F, Shertzer H G
Exp Lung Res. 1983 Dec;5(4):259-68. doi: 10.3109/01902148309061519.
A method is described for preparing and maintaining an isolated perfused and ventilated mouse lung. The preparation is especially suited for studying xenobiotic metabolism or toxicological interactions, in a species with a broad spectrum of studies in pulmonary toxicology. The preparation is viable with respect to drug metabolism for up to two hours, as judged from studies of aniline oxidation to p-aminophenol. With [14C]-benzo(a)pyrene as substrate for the lungs of male ICR Swiss mice, the major ethyl acetate-extractable metabolites are the 3-hydroxy, 9,10-dihydrodiol, 7,8-dihydrodiol, and 4,5-dihydrodiol derivatives. The rates of individual BaP metabolite production are increased in lungs from mice pretreated with Aroclor 1254 or beta-naphthoflavone, substances known to induce increased synthesis of cytochrome P-450. Small amounts of water-soluble BaP metabolites were hydrolyzed by beta-glucuronidase and aryl sulfatase, suggesting the presence of enzymes required for these conjugations. These results support the existence of significant cytochrome P-450-dependent and conjugative BaP metabolism in the intact mouse lung, similar to that examined in other species, and capable of contributing to the systemic metabolism of this carcinogen.
本文描述了一种制备和维持分离的灌注和通气小鼠肺的方法。该制备方法特别适用于在肺毒理学研究广泛的物种中研究外源性物质代谢或毒理学相互作用。从苯胺氧化为对氨基酚的研究判断，该制备物在药物代谢方面可持续长达两小时。以[14C] -苯并(a)芘作为雄性ICR瑞士小鼠肺的底物，主要的乙酸乙酯可提取代谢物是3 -羟基、9,10 -二氢二醇、7,8 -二氢二醇和4,5 -二氢二醇衍生物。用Aroclor 1254或β -萘黄酮预处理的小鼠肺中，单个BaP代谢物的产生速率增加，已知这两种物质可诱导细胞色素P - 450合成增加。少量水溶性BaP代谢物可被β -葡萄糖醛酸酶和芳基硫酸酯酶水解，表明存在这些结合所需的酶。这些结果支持完整小鼠肺中存在显著的细胞色素P - 450依赖性和结合性BaP代谢，类似于在其他物种中检测到的情况，并且能够促进这种致癌物的全身代谢。
