CELLULAR-DAMAGE BY FERRIC NITRILOTRIACETATE AND FERRIC CITRATE IN V79-CELLS - INTERRELATIONSHIP BETWEEN LIPID-PEROXIDATION, DNA STRAND BREAKS AND SISTER CHROMATID EXCHANGES

Ferric nitrilotnacetate (Fe-NTA) and ferric citrate (Fe-citrate) were used to study the cellular damage mediated by iron overload with respect to cytotoxicity, lipid peroxidation, DNA strand breaks and sister chromatid exchanges (SCE). At non-toxic concentrations, Fe-NTA induced lipid peroxidation, DNA strand breaks and SCE in a dose- and time-dependent manner. Comparing the time courses of the different events, the increase in lipid peroxidation seems to be associated with the generation of DNA strand breaks, since both types of cellular damage were observed after 1 - 3 h of incubation. In contrast, the induction of SCE was low after 24 h and increased after 48 and 72 h treatment, indicating the requirement of other types of DNA damage. Fe-citrate was inactive in the induction of lipid peroxidation and SCE, and no significant number of DNA strand breaks were generated, as determined by the alkaline unwinding method. Our results suggest that the induction of lipid peroxidation and DNA strand breaks by iron overload depend on special features of the iron complex applied, while the chromosomal and genetic effects require site specific DNA damage dependent on intracellular iron metabolism. It is concluded that iron overload is able to induce genetic damage in intact cells provided that iron is present in a bioavailable form.