MANGANESE SUPEROXIDE-DISMUTASE IN HUMAN PLEURAL MESOTHELIOMA CELL-LINES

Mesothelioma is a malignant pleural or intraperitoneal tumor attributa ble to asbestos exposure in more than 80% of the cases. Manganese supe roxide dismutase (MnSOD), a mitochondrial superoxide radical scavengin g enzyme, is low in most tumors but is known to be induced by asbestos fibers and certain cytokines. Induction of MnSOD may be associated in asbestos-related pulmonary diseases in vivo. We investigated here MnS OD specific activity and MnSOD mRNA level using healthy human lung tis sue, SV40-transformed human pleural mesothelial cells (Met5A), and six human malignant mesothelioma cell line cells. Total SOD (CuZnSOD + Mn SOD) and MnSOD activities were 20.0 +/- 4.8 U/mg protein and 3.2 +/- 1 .2 U/mg protein in healthy human lung tissue, and 25.6 +/- 10.7 U/mg a nd 3.8 +/- 1.0 U/mg in Met5A cells, respectively. In four mesothelioma cell lines MnSOD activity was significantly elevated, the highest act ivity (30.1 +/- 8.2 U/mg) was almost 10-fold compared to the activity in Met5A cells. The steady state mRNA level of MnSOD was low in Met5A cells and markedly higher in all mesothelioma cell lines roughly in pr oportion with enzyme activities. Cytotoxicity experiments, which were conducted in four cell lines, indicated that cells containing high MnS OD mRNA level and activity were resistant to the mitochondrial superox ide-producing agent menadione. In conclusion, our results suggest that human mesothelioma may express high levels of MnSOD, which is associa ted with high oxidant resistance of these cells.