Effect of iron chelators on the cytotoxic and genotoxic action of hyperoxia in Chinese hamster ovary cells.
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 microM) 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 microM) 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 mechanism of toxicity by normobaric hyperoxia in CHO cells. However, the results may still be consistent with a critical involvement of particular iron fraction(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.
Gille
J J
JJ
Department of Human Genetics, Free University, Amsterdam, The Netherlands.
van Berkel
C G
CG
Joenje
H
H
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival; D002869:Chromosome Aberrations; D006224:Cricetinae; D003676:Deferoxamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010100:Oxygen / Q000037:antagonists & inhibitors*; D010618:Phenanthrolines / Q000494:pharmacology; D012854:Sister Chromatid Exchange
D007502:Iron Chelating Agents; D010618:Phenanthrolines; D006861:Hydrogen Peroxide; D003676:Deferoxamine; D010100:Oxygen; C025205:1,10-phenanthroline