Nickel impairs the repair of UV- and MNNG-damaged DNA.
Nickel(II) is reported to be genotoxic, but the mechanisms underlying its genotoxicity are largely unknown. It can interfere with DNA repair and this may contribute to its genotoxicity. We studied the effect of nickel chloride on the repair of DNA damaged by UV radiation or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) in human lymphocytes using the alkaline comet assay. Nickel(II) at 1 microM caused an accumulation of DNA breaks during repair incubation, which could follow from the inhibition of the polymerization/ligation step of UV-damaged DNA repair. On the other hand, nickel(II) inhibited the formation of transient DNA breaks brought by the repair process after incubation with MNNG at 5 microM, which might follow from interference with the recognition/incision step of excision repair. Additionally, nickel at 1 microM inhibited the activity of formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (Alk A), enzymes involved in DNA excision repair. A decrease in endonuclease III (Endo III) activity was observed at 2 and 5 microM of nickel chloride. Our results suggest that nickel(II) at non-cytotoxic concentrations can inhibit various steps of DNA excision repair, and this may contribute to its genotoxicity.
Woźniak
Katarzyna
K
Department of Molecular Genetics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.
Błasiak
Janusz
J
D000328:Adult; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity*; D014466:Ultraviolet Rays
D008769:Methylnitronitrosoguanidine; C022838:nickel chloride; D009532:Nickel