Solubilization of the carcinogen nickel subsulfide and its interaction with DNA and protein

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Abstract
Significant concentrations (1-10 mM) of nickel(II) were found in solution after incubation of the potent carcinogen nickel subsulfide in 0.05 M Tris-HCl, pH 7.4, solutions containing DNA, rat liver microsomes, and NADPH. The presence of NADPH decreased the rate of solubilization of nickel subsulfide. The solubilized Ni exhibited electronic absorption spectra and magnetic moments characteristic of octahedral nickel(II). The solubilized nickel(II) bound to DNA with an apparent equilibrium constant of 730 M-1 and with a saturation binding value of 1 nickel per 2.4 nucleotides. Microsomes lowered the saturation binding of Ni to DNA but dramatically increased the amount of Ni-DNA complex stable to precipitation with salt and poly-(ethylene glycol). The amount of protein associated with DNA precipitated from protein-extracted solutions correlated with the amount of Ni bound to DNA. Microsomes may mediate the binding of Ni to DNA by forming a stable ternary protein-nickel(II)-DNA complex.