Decreased expression of manganese superoxide dismutase mRNA and protein after immortalization and transformation of mouse liver cells.

Altered levels of superoxide dismutase (SOD), the enzyme that scavenges toxic superoxide anion produced during normal metabolism or after oxidative insult, have been implicated in multistage carcinogenesis of both rodents and humans. Using a mouse liver cell model, we report here that after cellular immortalization, both copper- and zinc-containing superoxide dismutase (Cu,ZnSOD) and manganese superoxide dismutase (MnSOD) activities decreased dramatically and that cellular transformation further decreased MnSOD but not Cu,ZnSOD activity. Decreased enzyme activities seen in transformed cells (Tx) were due to decreased amounts of immunoreactive enzyme protein that results from decreased superoxide dismutase mRNA expression. This downregulation of gene expression may occur at the transcriptional level, as suggested by results with cycloheximide (Chx) and actinomycin D (AcD) treatments.