POSTTRANSCRIPTIONAL INHIBITION OF ORNITHINE DECARBOXYLASE INDUCTION BY ZINC IN A DIFLUOROMETHYLORNITHINE RESISTANT CELL-LINE

Addition of Zn2+ to cell medium inhibited the induction of ornithine decarboxylase (ODC) activity in ODC overproducing L1210-DFMO(r) cells. A significant effect was observed at a concentration as low as 0.01 mM, however a more marked inhibition was caused by the addition of 0.1 mM Zn2+. The inhibition of the induction of ODC activity was accompanied by a proportional decrease in the content of immunoreactive ODC protein, whereas the level of ODC mRNA, determined by a solution hybridization RNase protection assay, was not affected significantly. Instead, some acceleration of ODC turnover was observed. The addition of 0.1 mM Co2+ Or Mn2+, but not of other divalent metal ions, also inhibited ODC induction; differently from Zn2+ however, these metals affected cell viability and/or cell growth. Removal of endogenous Zn2+ by a chelator also provoked a strong decrease of ODC induction, which was reversed by Zn2+. However, addition of Zn2+ in excess of the chelator proved to be markedly inhibitory. These results indicate that both a restricted Zn2+ availability and an enhanced presence of the metal can inhibit the induction of ODC in L1210-DFMO(r) cells.