Solubilization of the Carcinogen Nickel Subsulfide and Its Interaction with Deoxyribonucleic Acid and Protein

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 nickel 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 one nickel per 2.4 nucleotides. Microsomes lowered the saturation binding of nickel to DNA but dramatically increased the amount of nickelDNA 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 nickel bound to DNA. These results suggest that microsomes mediate the binding of nickel to DNA by forming a stable ternary protein-nickel(II)-DNA complex.