Van Winkle Laura S, Gunderson Andrew D, Shimizu Judith A, Baker Gregory L, Brown Collette D
Department of Anatomy, School of Veterinary Medicine, University of California-Davis, Davis, California 95616-8732, USA.
Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L1122-34. doi: 10.1152/ajplung.00309.2001.
Humans are widely exposed to polycyclic aromatic hydrocarbons, commonly found in cigarette smoke and diesel exhaust. These can undergo site- and cell-specific metabolism to cytotoxic intermediates. Metabolism of naphthalene and Clara cell cytotoxicity have been extensively studied in male animals. To address whether male and female mice are equally susceptible to naphthalene, mice were injected with naphthalene, and lungs were examined 1, 2, 3, 6, and 24 h after treatment. By analysis of acute injury using differential permeability to fluorescent nuclear dyes and high-resolution histopathology, injury in female mice was found to be more extensive, occur earlier, and include permeable cells in proximal airways, including airway bifurcations. HPLC analysis of the products of cytochrome P-450 (CYP)-mediated metabolism in microdissected airways indicated that although both genders produced a predominance of products from CYP2F2, female mice produced more naphthalene dihydrodiol in distal airways, the primary sites of injury. We conclude that there are clear gender differences in susceptibility to naphthalene-induced injury and that differences in metabolism of naphthalene may play a role in elevated susceptibility in female mice.
人类广泛接触多环芳烃，这种物质常见于香烟烟雾和柴油废气中。它们可进行位点和细胞特异性代谢，生成细胞毒性中间体。萘的代谢及克拉拉细胞的细胞毒性已在雄性动物中得到广泛研究。为探讨雄性和雌性小鼠对萘的易感性是否相同，给小鼠注射萘，并在处理后1、2、3、6和24小时检查肺部。通过使用对荧光核染料的差异通透性和高分辨率组织病理学分析急性损伤，发现雌性小鼠的损伤更广泛、出现更早，且包括近端气道（包括气道分支）中的可渗透细胞。对显微切割气道中细胞色素P - 450（CYP）介导的代谢产物进行高效液相色谱分析表明，尽管两性均主要产生CYP2F2的产物，但雌性小鼠在远端气道（主要损伤部位）产生更多的萘二氢二醇。我们得出结论，萘诱导损伤的易感性存在明显的性别差异，且萘代谢的差异可能在雌性小鼠易感性升高中起作用。
