Boyd M R, Statham C N, Longo N S
J Pharmacol Exp Ther. 1980 Jan;212(1):109-14.
Oral administration of carbon tetrachloride to rats or mice caused striking decreases in rat lung microsomal cytochrome P-450 and benzphetamine demethylase activity and in the enzyme-mediated covalent binding of 4-ipomeanol in preparations of rat and mouse lung microsomes, mouse lung slices and isolated whole-mouse lungs. Although it is not yet known whether cytochrome P-450 and benzphetamine demethylase activities are present in substantial amounts in more than one lung cell type in mice or rats, previous studies have indicated that cytochrome P-450 enzymes located in pulmonary bronchiolar Clara cells of these mediate the covalent binding of 4-ipomeanol to lung macromolecules. Histologic examinations of lungs of animals given doses of CCl4, orally or by inhalation, revealed striking morphologic changes in Clara cells, including severe dilation of endoplasmic reticulum and occasional cellular necrosis. Because of cytochrome P-450 enzymes are capable of mediating the formation of highly reactive and potentially toxic-free radicals from CCl4, the present results support the view that pulmonary Clara cells are susceptible to CCl4-induced injury due to their capacity to metabolically activate the chemical.
给大鼠或小鼠口服四氯化碳，会使大鼠肺微粒体细胞色素P - 450和苄非他明脱甲基酶活性显著降低，同时也会使大鼠和小鼠肺微粒体、小鼠肺切片及离体全小鼠肺制剂中4 - 异薄荷醇的酶介导共价结合显著减少。虽然目前尚不清楚细胞色素P - 450和苄非他明脱甲基酶活性在大鼠或小鼠的多种肺细胞类型中是否大量存在，但先前的研究表明，位于这些动物肺细支气管克拉拉细胞中的细胞色素P - 450酶介导4 - 异薄荷醇与肺大分子的共价结合。对经口或吸入给予四氯化碳剂量的动物肺部进行组织学检查，发现克拉拉细胞有显著的形态学变化，包括内质网严重扩张和偶尔的细胞坏死。由于细胞色素P - 450酶能够介导四氯化碳形成高反应性和潜在毒性的自由基，目前的结果支持这样一种观点，即肺克拉拉细胞因其代谢激活该化学物质的能力而易受四氯化碳诱导的损伤。
