Influence of Adriamycin and paraquat on antioxidant enzyme expression in primary rat hepatocytes

The cytostatic Adriamycin and the herbicide paraquat form reactive oxygen s pecies during enzymatic activation. Adriamycin, but not paraquat, is also a ble to intercalate into DNA and to interfere with DNA synthesis and transcr iption. We investigated the influence of both substances on antioxidant enz yme expression in primary rat hepatocytes. Treatment of hepatocytes with Ad riamycin led to an increase in catalase and a decrease in MnSOD mRNA expres sion. In contrast, exposure of hepatocytes to paraquat resulted in an incre ase in both catalase and MnSOD message levels. CuZnSOD mRNA was not respons ive to either treatment. Adriamycin almost completely inhibited RNA synthes is, but paraquat did not change either RNA or protein synthesis. Both subst ances induced lipid peroxidation as measured by the accumulation of malondi aldehyde in the medium. These findings indicate that catalase and MnSOD are not regulated co-ordinately in hepatocytes and that ROS-producing agents c an differentially influence expression of antioxidant enzymes depending on their capacity to inhibit transcription.