Induction of oxidative DNA damage by ferric iron in mammalian cells

• Published in: Carcinogenesis (New York) 1995-12, Vol.16 (12), p.3009-3013
• Main Authors: Hartwig, Andrea, Schlepegrell, Regina
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Line; Cell Survival - drug effects; Chemical agents; Cricetinae; Cricetulus; DNA Damage; Ferric Compounds - toxicity; Medical sciences; Mutagens - toxicity; Nitrilotriacetic Acid - analogs & derivatives; Nitrilotriacetic Acid - toxicity; Oxidation-Reduction; Tumors
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/16.12.3009

Ferric nitrilotriacetate (Fe-NTA) and ferric citrate (Fe-citrate) were compared with respect to their potential to induce oxidative DNA damage in V79 Chinese hamster cells. DNA base modifications, including 8-hydroxyguanine (7,8-dihydro-8-oxoguanine), were quantified by the frequency of lesions recognized by the bacterial Fpg protein (formamidopyrimidine-DNA glycosylase) in combination with the alkaline unwinding assay. Fe-NTA induced oxidative DNA damage in a time- and dose-dependent manner, yielding significant increases in Fpg-sensitive sites above background after incubation for 24 or 48 h with 500 and 250 μM respectively. At both time points the frequency of DNA base modifications exceeded the number of DNA strand breaks. In contrast, neither DNA strand breaks nor Fpg-sensitive sites were detected after treatment with Fecitrate at concentrations up to 2 mM for 24 or 48 h; this inactivity of Fe-citrate was independent of the molar ratio of iron to ligand (1:1, 1:2, 1:10 or 1:20). The results indicate that the cellular damage induced by ferric iron depends strongly on the actual complex applied, possibly due to differences in the intracellular distribution, which in turn may affect the availability of iron for redox reactions at or in close proximity to the DNA.