Consequences of aberrant ornithine decarboxylase regulation in rat hepatoma cells

Margaret E. Tome, Steven M. Fiser, Eugene W. Gerner

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

DH23A cells, an α‐difluoromethylornithine (DFMO)–resistant variant of rat hepatoma tissue culture cells (HTC), contain high levels of very stable ornithine decarboxylase (ODC). In the absence of DFMO, the high ODC activity results in a large accumulation of endogenous putrescine. Concomitant with the putrescine increase is a period of cytostasis and a subsequent loss of viable cells. In contrast, HTC cells with a moderate polyamine content can be maintained in exponential growth. This suggests that a moderate polyamine concentration is necessary for both optimal cell growth and survival. The cytoxicity observed in the DH23A cells is apparently not due to byproducts of polyamine oxidation or alterations in steady state intracellular pH or free [Ca2+]. It is possible to mimic the effects of high levels of stable ODC by treatment of cells with exogenous putrescine in the presence of DFMO. This suggests that overaccumulation of putrescine is the causative agent in the observed cytotoxicity, although the mechanism is unclear. These data support the hypothesis that downregulation of ODC may be necessary to prevent accumulation of cytotoxic concentrations of the polyamines. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalJournal of Cellular Physiology
Volume158
Issue number2
DOIs
StatePublished - Feb 1994

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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