Video Time-Lapse Microscopy of Phagocytosis and Intracellular Fate of Crystalline Nickel Sulfide Particles in Cultured Mammalian Cells1

The endocytosis and intracellular distribution of carcinogenic crystalline nickel sulfide (NiS) particles in Chinese hamster ovary cells were studied using time-lapse video recording with phase-contrast and bright-field optics. Crystalline NiS particles were phagocytosed by Chinese hamster ovary cells in regions of membrane ruffling. While these particles may remain bound to the cell surface for variable time intervals (min to hr), their internalization generally required only 7 to 10 min. Endocytosed crystalline NiS particles exhibited saltatory motion, and lysosomes were observed to interact repeatedly with the par ticles in a manner similar to that observed during the digestion of macropinosomes. Particles were never observed to be exocytosed from the cell, and with time, most of the internalized particles aggregated in the region around the nucleus. After 24 to 48 hr, particle saltation decreased to a point where the particle position became relatively fixed in the perinuclear region, and in some instances, this was associated with a conspicuous vacuole formation around the particles. It is con cluded that the uptake and distribution of crystalline NiS par ticles occur by normal endocytic and saltatory processes as occur during the formation and breakdown of macropino somes. The observed lysosomal interaction with phagocytosed cytoplasmic NiS may accelerate particulate nickel dissolution allowing entry of ionic nickel into the nucleus.