Factors influencing the phagocytosis, neoplastic transformation, and cytotoxicity of particulate nickel compounds in tissue culture systems

Seven particulate nickel compounds were studied for their cell transformation activity using cultured Syrian hamster embryo cells and for their phagocytotic activity in cultured Chinese hamster ovary cells. The crystalline nickel compounds (αNi3S2, αNiS, and Ni3Se2) had significantly more cell transforming activity and were more actively phagocytized than the other nickel compounds examined (amorphous NiS, metallic Ni, Ni3O2, and NiO). Therefore, the crystalline structure of nickel compounds is one factor influencing their toxic activity upon biological systems. A second influencing factor was the particle size of the water-insoluble nickel compounds. Particles of crystalline αNiS ranging from 2 to 4 μm were phagocytized six times more than αNiS particles having mean diameters of 5-6 μm. Differences in amorphous NiS particle size had little effect on its already low susceptibility to be phagocytized by cells and ability to cause a reduction of cell plating efficiency. The presence of Mn dust inhibited the neoplastic transformation of crystalline nickel sulfide and also reduced the phagocytosis of crystalline αNiS and αNi3S2 particles by cultured cells. The phagocytosis of crystalline NiS particles was inhibited by the presence of amorphous NiS, Mn or MnCl2. Therefore, the presence of noncarcinogenic metals which are not themselves actively phagocytized diminishes the transforming effects of crystalline metal compounds probably by reducing their internalization. Various metabolic inhibitors such as dansylcadaverine, cycloheximide, and actinomycin D reduced the phagocytosis of crystalline αNiS.