Overproduction of human Mn-superoxide dismutase modulates paraquat-mediated toxicity in mammalian cells.

Manganese superoxide dismutase (MnSOD) is a nuclear encoded mitochondrial matrix enzyme that functions to scavenge superoxide radicals. The human MnSOD cDNA under the transcriptional control of a human beta-actin promoter was introduced into mouse C3H10T1/2 cells by cotransfection with a recombinant plasmid containing the NeoR selectable marker. C3H10T1/2 transformants (C3H-SOD) were obtained that expressed high levels of authentic enzymatically active human MnSOD. Overexpression of the MnSOD gene did not affect the protein levels of CuZnSOD, catalase (CAT), or glutathione peroxidase (GPX) in the transformants. Treatment of cells with paraquat was less toxic to the C3H-SOD cells than to the control cells. These results are consistent with the possibility that superoxide radicals are mediators of paraquat cytotoxicity.