Selective Phagocytosis of Crystalline Metal Sulfide Particles and DNA Strand Breaks as a Mechanism for the Induction of Cellular Transformation1

Crystalline NiS, CuS, CoS2, and CdS particles were actively phagocytosed by cells and potently induced morphological transformation of Syrian hamster embryo cells in a concentra tion-dependent fashion. In contrast, the respective amorphous metal sulfide particles (amorphous NiS, CuS, CoS, and CdS) were not as actively phagocytosed by cultured cells and, in comparison to the crystalline form of these compounds, in duced considerably less morphological transformation at both cytotoxic and noncytotoxic exposure levels. Chemical reduc tion of positively charged amorphous NiS with LiAIH4 resulted in active phagocytosis of these particles which was also asso ciated with enhancement of cellular transformation. Crystalline but not amorphous NiS caused considerable strand breaks in the DNA of Chinese hamster ovary cells following 2 to 3 hr exposure at 10 jug/ml as determined by alkaline sucrose gra dient techniques with subsequent determination of DNA molec ular weight. Phagocytized inert particles such as latex beads did not induce transformation or DNA damage, suggesting that genotoxic dissolution products such as Ni2+ rather than the phagocytized particles are responsible for the observed DNA damage and cellular transformation. NiCI2 was about one-third to one-half as potent in inducing cellular transformation com pared to crystalline NiS on a weight basis. These results correlate the selective phagocytosis of crystalline metal sulfides to their more potent activity in the induction of cellular transformation.