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Phagocytosis of nickel subsulfide particles during the early stages of neoplastic transformation in tissue culture.

Cellular uptake of crystalline Ni3S2 particles (a potent carcinogen) and amorphous NiS particles (a noncarcinogen) were studied using light and electron microscopy. Cultured Syrian hamster embryo cells and Chinese hamster ovary cells actively phagocytized Ni3S2 particles (less than or equal to 5 micrometer) but did not take up NiS particles (less than 5 micrometer). For example, within 30 min after addition of Ni3S2 (high dose) to cell cultures, 12.5% of the cells contained nickel particles in the cytoplasm. Within 6 hr, 75% of the cells had engulfed Ni3S2 particles. Cultures exposed to NiS under similar conditions had less than 1.0% of the cells containing particulate nickel within 6 hr. The uptake of Ni3S2 was related to the particle concentration and duration of exposure. Concentration-dependent morphological transformation was induced by Ni3S2 in Syrian hamster embryo cells, but similar treatment of cells with amorphous NiS resulted in no morphological transformation. Pretreatment of Syrian hamster embryo cells with benzopyrene enhanced the cellular uptake of Ni3S2 particles and also the incidence of Ni3S2-induced morphological transformation. Our results suggest that the carcinogenic activity of particulate Ni3S2 is related to its cellular uptake.