Induction of 8-hydroxy-2'-deoxyguanosine by cobalt(II) and hydrogen peroxide in vitro.
In order to test the effects of cobalt on oxidative DNA damage, we measured the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the presence of cobalt in calf thymus DNA and in DNA of human diploid fibroblasts. Treatment of calf thymus DNA with Co(II) at 500 microM hydrogen peroxide resulted in a dose-dependent increase in 8-OHdG, which culminated at 25 microM Co(II) (62.6 modified/10(5) dG) and declined at higher Co(II) concentrations [9.6 modified/10(5) dG at 250 microM Co(II)]. Incubation of calf thymus DNA with Co(II) alone did not cause an increase in 8-OHdG. Treatment of calf thymus DNA with H2O2, (0.25-2 mM) caused only a slight generation of 8-OHdG (2.7/10(5) dG, at 2 mM H2O2). Exposure of human diploid fibroblasts to Co(II) at 5-250 microM did not result in an increase in 8-OHdG in a dose-dependent manner, although treated cells showed significantly higher 8-OHdG levels than untreated controls (2.026 +/- 0.695 vs. 1.395 +/- 0.433 8-OHdG/10(5) dG) at all concentrations. Our data indicate that in the presence of H2O2, Co(II) stimulates the in vitro formation of 8-OHdG.
Ivancsits
Sabine
S
Department of Occupational Medicine, University of Vienna, Austria. Sabine.Ivancsits@akh-wien.ac.at
Diem
Elisabeth
E
Pilger
Alexander
A
Rüdiger
Hugo W
HW
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D004171:Diploidy; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*
D016877:Oxidants; D003035:Cobalt; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine