DECREASED EXPRESSION OF MANGANESE SUPEROXIDE-DISMUTASE MESSENGER-RNA AND PROTEIN AFTER IMMORTALIZATION AND TRANSFORMATION OF MOUSE-LIVER CELLS

Altered levels of superoxide dismutase (SOD), the enzyme that scavenge s toxic superoxide anion produced during normal metabolism or after ox idative insult, have been implicated in multistage carcinogenesis of b oth 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 (M nSOD) activities decreased dramatically and that cellular transformati on further decreased MnSOD but not Cu,ZnSOD activity. Decreased enzyme activities seen in transformed cells (Tx) were due to decreased amoun ts of immunoreactive enzyme protein that results from decreased supero xide 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.