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

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.