Oberley T D, Sempf J M, Oberley M J, McCormick M L, Muse K E, Oberley L W
Pathology and Laboratory Medicine Service, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705.
Virchows Arch. 1994;424(2):155-64. doi: 10.1007/BF00193495.
Analysis of activities of the antioxidant enzyme manganese superoxide dismutase in human renal cell carcinomas often showed greatly altered enzyme levels (either elevated or depressed) compared to the cell of origin, the kidney proximal tubule. In order to better understand the variability observed, immunogold studies were performed on human renal cell carcinomas using a polyclonal antibody to human kidney manganese superoxide dismutase. For comparison, studies were also performed using antibodies to other antioxidant enzymes. For histologic studies, renal cell carcinomas were subclassified on the basis of light microscopy and ultrastructural analysis into clear cell, granular cell, or mixed clear and granular cell variants. In all three types of tumor, immunogold studies showed little staining using antibodies to copper, zinc superoxide dismutase or glutathione-dependent enzymes. However, intensity of labeling for manganese superoxide dismutase and catalase depended on the cell type(s) in the tumor. Clear cell variants demonstrated trace staining for manganese superoxide dismutase and catalase, while granular cell variants exhibited heavy staining for both of these enzymes. Mixed types of tumors showed clear cells with trace staining for all antioxidant enzymes examined, while granular cells again showed intense labeling for manganese superoxide dismutase and catalase. Using normal kidney proximal tubule as a comparison, immunogold ultrastructural analysis using antibody to manganese superoxide dismutase demonstrated infrequent small lightly labeled mitochondria in clear cell variants, while granular cell variants exhibited numerous medium-sized heavily labeled mitochondria. These data suggest that: 1) the variability in activity values for manganese superoxide dismutase may be due to heterogeneity of cell types in these tumors and 2) manganese superoxide dismutase immunoreactive protein was elevated in granular cells both because of an increase in number of mitochondria and because the labeling density in mitochondria was increased compared to mitochondria in clear cell types or in normal proximal tubular cells.
对人类肾细胞癌中抗氧化酶锰超氧化物歧化酶活性的分析表明，与起源细胞肾近端小管相比，该酶水平常常发生极大改变（升高或降低）。为了更好地理解所观察到的变异性，使用针对人类肾脏锰超氧化物歧化酶的多克隆抗体对人类肾细胞癌进行了免疫金研究。作为对照，也使用针对其他抗氧化酶的抗体进行了研究。对于组织学研究，根据光学显微镜和超微结构分析，将肾细胞癌分为透明细胞型、颗粒细胞型或透明细胞与颗粒细胞混合型。在所有这三种肿瘤类型中，免疫金研究显示，使用针对铜锌超氧化物歧化酶或谷胱甘肽依赖性酶的抗体时几乎没有染色。然而，锰超氧化物歧化酶和过氧化氢酶的标记强度取决于肿瘤中的细胞类型。透明细胞型对锰超氧化物歧化酶和过氧化氢酶显示微量染色，而颗粒细胞型对这两种酶均显示强染色。混合型肿瘤中，透明细胞对所有检测的抗氧化酶显示微量染色，而颗粒细胞再次对锰超氧化物歧化酶和过氧化氢酶显示强标记。以正常肾近端小管作为对照，使用针对锰超氧化物歧化酶的抗体进行免疫金超微结构分析显示，透明细胞型中偶尔有少量轻度标记的线粒体，而颗粒细胞型中有大量中等大小的重度标记的线粒体。这些数据表明：1）锰超氧化物歧化酶活性值的变异性可能归因于这些肿瘤中细胞类型的异质性；2）颗粒细胞中锰超氧化物歧化酶免疫反应性蛋白升高，这既是因为线粒体数量增加，也是因为与透明细胞型或正常近端小管细胞中的线粒体相比，线粒体中的标记密度增加。
