Zinc is required for the expression of ornithine decarboxylase in a difluoromethylornithine-resistant cell line.
Dilution of quiescent L1210-DFMOr (difluoromethylornithine-resistant) cells in fresh medium containing serum led to the induction of ornithine decarboxylase (ODC) and to the expression of its mRNA, as determined by a sensitive solution-hybridization-RNase-protection assay. Addition of the chelating agent diethylenetriaminepentaacetic acid (DTPA) at seeding time caused an inhibition of the induction of ODC activity by up to 90%, and only Zn2+ of the bivalent metal ions tested was effective in reversing this effect. The inhibition of the induction of ODC activity was accompanied by a marked decrease, prevented by Zn2+ supplementation, of the accumulation of immunoreactive ODC protein and ODC mRNA. DTPA treatment also caused a slight acceleration of ODC turnover. These results indicate that a restricted Zn2+ availability in L1210-DFMOr cells impairs ODC induction remarkably, mainly by affecting the expression of the messenger.
Flamigni
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F
Dipartimento di Biochimica, Università di Bologna, Italy.
Campana
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G
Carboni
L
L
Guarnieri
C
C
Spampinato
S
S
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004351:Drug Resistance; D000518:Eflornithine / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D007939:Leukemia L1210 / Q000201:enzymology*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D004369:Pentetic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D012333:RNA, Messenger; D004369:Pentetic Acid; D007501:Iron; D009955:Ornithine Decarboxylase; D015032:Zinc; D000518:Eflornithine