Zinc salts differentially modulate DNA damage in normal and cancer cells.
Zinc plays an essential role in a wide range of cellular processes, including defense against free radicals and maintaining genomic stability. The presence of zinc in some proteins is fundamental for their functioning as transcription factors. Little is known about interaction between zinc and DNA, which can be important in light of reports on the role of zinc in cancer transformation and sometimes contradictory character of these reports. In the present study we studied cyto- and genotoxicity of zinc sulfate (ZnSO(4)) in normal human lymphocytes and human myelogenous leukemia K562 cancer cells in the presence of zinc and hydrogen peroxide (H(2)O(2)). Zinc at concentrations from the range 10-1000 microM decreased the viability of cancer cells and this effect, especially for low concentrations of the element, was much more pronounced than in normal cells. Zinc did not induce DNA damage in normal cells, but did so in cancer cells. We observed a key difference between the action of zinc in normal and cancer cells in the presence of H(2)O(2), since the element exerted a protective effect against cyto- and geno-toxic action of H(2)O(2) in the former, whereas it increased such action in the latter. Zinc inhibited the repair of DNA damage induced by H(2)O(2) in cancer cells. The results suggest that zinc may protect normal cells against DNA-damaging action and increase this action in cancer cells, which indicates the dual action of this element in dependency of target cells and can be useful in cancer therapy.
Sliwinski
Tomasz
T
Department of Molecular Genetics, University of Lodz, Lodz, Poland.
Czechowska
Agnieszka
A
Kolodziejczak
Magdalena
M
Jajte
Jolanta
J
Wisniewska-Jarosinska
Maria
M
Blasiak
Janusz
J
D000328:Adult; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology / Q000633:toxicity; D020014:K562 Cells; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000378:metabolism; D019287:Zinc Sulfate / Q000494:pharmacology* / Q000633:toxicity
D019287:Zinc Sulfate; D006861:Hydrogen Peroxide