Overproduction of human Cu/Zn-superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation.

Abstract

The ‘housekeeping’ enzyme Cu/Zn‐superoxide dismutase (SOD‐1) is encoded by a gene residing on human chromosome 21, at the region 21q22 known to be involved in Down's syndrome. The SOD‐1 gene and the SOD‐1 cDNA were introduced into mouse L‐cells and human HeLa cells, respectively as part of recombinant plasmids containing the neoR selectable marker. Human and mouse transformants were obtained that expressed elevated levels (up to 6‐fold) of authentic, enzymatically active human SOD‐1. This enabled us to examine the consequences of hSOD‐1 gene dosage, apart from gene dosage effects contributed by other genes residing on chromosome 21. Human and mouse cell clones that overproduce the hSOD‐1 had altered properties; they were more resistant to paraquat than the parental cells and showed an increase in lipid peroxidation. The data are consistent with the possibility that gene dosage of hSOD‐1 contributes to some of the clinical symptoms associated with Down's syndrome.