Abstract
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 particles 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 concluded that the uptake and distribution of crystalline NiS particles occur by normal endocytic and saltatory processes as occur during the formation and breakdown of macropinosomes. The observed lysosomal interaction with phagocytosed cytoplasmic NiS may accelerate particulate nickel dissolution allowing entry of ionic nickel into the nucleus.
Primary funding for this research project was provided by the Office of Research and Development, Environmental Protection Agency, under Grant R-808048. Additional funding was provided by Research Training Grant ES07090 from the National Institute of Environmental Health Sciences and by Research Contract DE-AS05-81 ER 60016 from the United States Department of Energy. The Environmental Protection Agency does not necessarily endorse any commercial products used in this study, and the conclusions represent the views of the authors and do not necessarily represent the opinions, policies, or recommendations of the Environmental Protection Agency. Additional support was provided by American Cancer Society Grant BC 334, and National Institute of Health Grant AM27078.
RSS Feeds