THE TRANSCRIPTIONAL REPRESSION OF THE HUMAN CU ZN SUPEROXIDE DISMUTASE(SOD1) GENE BY THE ANTICANCER DRUG, MITOMYCIN C(MMC)/

The Cu/Zn superoxide dismutase(sod1) is one of the key enzymes that pr otects cells against oxidative stress. In order to investigate the eff ects of mitomycin C(MMC) on the induction of apoptotic cell death and on the sod1 transcription level, the CATs activity of HepG2 cells tran sfected with sod1 promoter-CAT(chloramphenicol acetyl transferase) fus ion reporter was measured after MMC treatment. The CAT assay showed th at exposure of HepG2 cells to MMC decreased the transcription level of the sod1 gene. The accumulation of p53 tumor suppressor protein by MM C treatment of HepG2 cells was noted. In order to investigate the p53- negative response element in its promoter region, a p53 cotransfection experiment with serially deleted sod1 promoter/CAT reporter construct s was performed. The results show a significant reduction of CAT activ ity in all deletion reporter constructs. The results show that MMC tre atment inhibited sod1 gene transcription through p53-mediated transcri ptional repression.