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Influence of Surface Charge and Dissolution on the Selective Phagocytosis of Potentially Carcinogenic Particulate Metal Compounds¹

Department of Pharmacology, University of Texas Medical School at Houston, Houston, Texas 77025

Substantial evidence has accumulated which documents the active endocytosis by cells of particulate nickel compounds having potent carcinogenic and transforming capacity; compounds less potent in these respects exhibit a reduced tendency to be phagocytized by cultured fibroblasts. The surface charges ( potentials) of a number of particulate nickel compounds were measured in an attempt to identify the determinants of their variable degrees of cellular uptake. The carcinogenic particulates, crystalline NiS, Ni₃S₂, and NiO, exhibit strongly negative potentials in distilled water and enter cells readily, while noncarcinogenic amorphous NiS, which is phagocytized to a lesser degree, is slightly positive in surface charge under similar conditions. The greater dissolution rate of amorphous NiS in comparison to crystalline NiS may contribute to its reduced uptake by cells by causing substantial alteration of the particle surface and/or by the generation of particle dissolution products at its site of cellular interaction which inhibit particle uptake. Addition of ionic nickel was found to be inhibitory toward the phagocytosis process in general, although the potency of ionic nickel in inhibiting particle uptake is not sufficiently high to attribute the selectivity of uptake of nickel-containing particulates solely to this inhibitory effect. Freshly suspended amorphous NiS particles were phagocytized more than particles aged in either H₂O or culture medium for 1 to 7 days. This reduced tendency of the aged amorphous NiS particles to be phagocytized remained following removal of potential inhibitory dissolution products. Binding of amorphous NiS to DEAE paper, which represented an alternate method to determine the surface charge, was decreased by aging in H₂O or culture medium, suggesting that a loss of negative surface charge during this aging process may have been associated with decreased uptake. These findings lend support to the hypothesis that surface charge may play a role in the phagocytosis of potentially carcinogenic nickel sulfide particles.

¹ Primary support was provided by Grant CA 29581 from the National Cancer Institute. Additional funding for this research project was provided by the Office of Research and Development, Environmental Protection Agency, under Grant R-808048, by Research Training Grant ES07090 from the National Institute of Environmental Health Sciences, and by Research Contract DE-AS05-81ER60016 from the United States Department of Energy.

² To whom requests for reprints should be addressed.

Received 12/27/82. Accepted 8/19/83.