Effect of iron chelators on the cytotoxic and genotoxic action of hyperoxia in Chinese hamster ovary cells

J. J.P. Gille, C. G.M. Van Berkel, H. Joenje*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The iron chelators o-phenanthroline and desferrioxamine were tested for their ability to protect Chinese hamster ovary cells against the cytotoxic and genotoxic effects of normobaric hyperoxia. Desferrioxamine added at sub-toxic concentrations (up to 2.5 μM) over a period of several days had no protective effect on hyperoxia-induced clonogenic cell killing and growth inhibition. The clastogenic effect of hyperoxia was strongly potentiated by desferrioxamine, while the induction of sister-chromatid exchanges (SCEs) by hyperoxia was unaffected. Similarly, o-phenanthroline (up to 0.25 μM) had no protective effect on hyperoxia-induced cell killing, growth inhibition, and SCE induction, while also this compound potentiated the clastogenic effect of hyperoxia. These results do not support a critical role for cellular iron in the mechanisms of toxicity by normobaric hyperoxia in CHO cells. However, the results may still be consistent with a critical involvement of particular iron fractions(s) not susceptible to the chelators used. Furthermore, our results show that concentrations of iron chelators known to protect against short-term (up to 1 h) toxic exposure to oxidative stress become toxic themselves when applied chronically, i.e., in the order of days.

Original languageEnglish
Pages (from-to)31-39
Number of pages9
JournalMutation Research DNAging
Issue number1
Publication statusPublished - Jan 1992

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