SUPEROXIDE-DISMUTASE AND SUPEROXIDE RADICAL IN MORRIS HEPATOMAS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (10) , 3686-3693
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 3 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. The Mn SOD specific activity was similar to the total SOD specific activity of isolated mitochondria, indicating that mitochondrial SOD is almost entirely Mn 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. Superoxide radical .**GRAPHIC**. formation was measured in submitochondrial particles obtained by sonication of isolated mitochondria and subsequent washings to remove the SOD. At least part of the mitochondrial SOD might be associated with the mitochondrial membrane. In liver submitochondrial particles, .**GRAPHIC**. 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 .**GRAPHIC**. production (slow- and fast-growth rates), radical formation was detected in the presence of succinate even when no inhibitor was present. Antimycin A stimulated the production of .**GRAPHIC**. in normal rat liver and slow-growth-rate tumor, but not in fast-growth-rate tumor submitochondrial particles. Reduced NAD did not lead to the production of .**GRAPHIC**. 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.