OSTEOTOXICITY OF CADMIUM AND LEAD IN HOS-TE-85 AND ROS-17 2.8 CELLS -RELATION TO METALLOTHIONEIN INDUCTION AND MITOCHONDRIAL BINDING/

Epidemiological, experimental and clinical data indicate that cadmium and lead are osteotoxins in man and other species. The relative sensit ivities of a clonal human osteosarcoma cell line (HOS TE 85) and a clo nal rat osteosarcoma cell line (ROS 17.28) to the cytotoxic effects of cadmium and lead were tested in serum-free media without added growth factors. The rat osteosarcoma cells were more sensitive to cadmium wi th cytotoxicity and inhibition of proliferation at 0.25 versus 0.75 an d 1.0 mumol l-1 cadmium, respectively, for human osteosarcoma cell lin es. The lower sensitivity to cadmium of human osteosarcoma cells is at tributed, at least partly, to induction of metallothionein synthesis b y cadmium and zinc in this cell line; in the rat osteosarcoma cell lin e, they do not induce metallothionein synthesis. Human osteosarcoma ce lls were more sensitive than rat osteosarcoma cells to lead with inhib ition (IC50) of proliferation at 4 mumol l-1 lead and cytotoxicity at 20 versus 6 and over 20 mumol l-1 lead, respectively, for these variab les in rat osteosarcoma cells. Both cells lines attained the highest l ead concentration in the 15000 x g (mitochondrial) fraction. The lead in the mitochondrial, microsomal, nuclear and cytosolic fractions of t he human cell line did not decrease during 24 h post-washout. Binding of lead was much less stable in the less sensitive rat cells, with 50- 100% loss of mitochondrial, microsomal and nuclear lead during 24 h po st-washout.