DNA strand breaks and poly (ADP-ribose) polymerase activation induced by crystalline nickel subsulfide in MRC-5 lung fibroblast cells

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Abstract
Nickel compounds are potent carcinogens. Their carcino genicity is believed to be associated with their solubility and cellular uptake. In the present study, we assessed the in vitro genotoxic effect of a water-insoluble nickel compound, crystalline nickel subsulfide (α-Ni 3S2) on human embryo lung fibroblast cell line (MRC-5 cells). DNA strand breaks was evaluated using single cell gel electrophoresis, or comet assay. The α-Ni3S2 induction of poly (ADP-ribose) polymerase (PADPRP), a nuclear enzyme associated with DNA damage and repair was also studied. Hydrogen peroxide (H2O2) was used as a reference compound. A dose-response relationship was found between α-Ni 3S2 concentrations (2.5 μg/cm2 to 20 μg/cm 2) and the comet tail length. The increase of PADPRP activity of α-Ni 3S2 treated MRC-5 cells was also significant and dose-dependent within the concentration range of 2.5 μg/ cm2 to 10 μg/cm 2. Close associations have been found between the comet length and PADPRP level for H2O2 (r=0.98) and α-Ni3S 2 (r=0.97). These results clearly suggest that α-Ni3S 2 is a potent agent in inducing DNA strand breaks, which may be closely related to its carcinogenic effects. Data from the present study also suggest that both comet assay and PADPRP determination are sensitive techniques for quantitative evaluation of DNA damage induced by nickel compounds.