title: Superoxide dismutase and superoxide radical in Morris hepatomas.
abstract: Total superoxide dismutase (SOD) and manganese superoxide dismutase (Mn SOD) specific activities were measured in tissue homogenates and in isolated mitochondria from normal rat liver and three Morris hepatomas of different growth rates. Total SOD and Mn SOD specific activities were decreased in all tumor homogenates when compared to normal liver; the lowest activity was associated with the fastest growing tumor. These results are consistent with the hypothesis that total Mn SOD specific activity is decreased in all tumors. The Mn SOD specific activity was similar to the total SOD specific activity of isolated mitochondria, indicating that mitochondrial SOD is almost entirely manganese containing. This activity was decreased in the fast- and medium-growth-rate hepatomas but was slightly increased in the tumor with the slowest growth rate when compared to liver. The normal or higher than normal mitochondrial Mn SOD specific activity indicates that decreased mitochondrial SOD specific activity is not a characteristic of all tumors. Superoxide radical (O2-.) formation was measured in submitochondrial particles obtained by sonication of isolated mitochondria and subsequent washings to remove the SOD. The difficulty encountered in reducing the SOD activity suggests that at least part of the mitochondrial SOD might be associated with the mitochondrial membrane. In liver submitochondrial particles, O2-. was formed only when succinate and antimycin A were used together, as substrate and inhibitor of the electron transport chain, respectively. In the hepatomas studied for O2-. production (slow- and fast-growth rates), the formation of the radical was detected in the presence of succinate even when no inhibitor was present. Antimycin A stimulated the production of O2-. in normal rat liver and slow-growth-rate tumor, but not in fast-growth-rate tumor submitochondrial particles. Reduced nicotinamide adenine dinucleotide did not lead to the production of O2-. by normal liver or hepatoma submitochondrial particles. Mitochondrial membrane damage was seen in micrographs of the medium- and fast-growing hepatomas. This could be a consequence of low mitochondrial SOD concomitant with a flux of superoxide, if the radical is produced in vivo by these mitochondria.
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005609:Free Radicals; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000648:ultrastructure; D008345:Manganese / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000648:ultrastructure; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D013386:Succinates / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism*; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*
chemical_list: D005609:Free Radicals; D013386:Succinates; D009243:NAD; D013481:Superoxides; D008345:Manganese; D013482:Superoxide Dismutase; D010100:Oxygen