TOXICITY OF CADMIUM TO RAT OSTEOSARCOMA CELLS (ROS-17-2.8) - PROTECTIVE EFFECT OF 1-ALPHA,25-DIHYDROXYVITAMIN-D3

Inadequate vitamin D intake is an important cofactor in clinical and experimental bone disease induced by chronic cadmium exposure. The interaction was investigated by culture of rat osteoblastic osteosarcoma cells (ROS 17 2.8) in a serum-free medium with equimolar concentrations of cadmium chloride and 1α,25-(OH)2 vitamin D3. After addition of cadmium alone to culture medium, the unstimulated secretion of osteocalcin and cellular alkaline phosphatase activity were inhibited at 10 pm, and of DNA synthesis and proline incorporation into collagen at 500 nm. In the presence of equimolar amounts of cadmium and 1α,25-(OH)2 vitamin D3, all four responses paralleled those of 1α,25-(OH)2 vitamin D3 alone up to the inhibitory concentration of 500 mm cadmium. Neither 10 nm 1α,25-(OH)2 vitamin D3 nor 1 μm cadmium induced synthesis of metallothionein in these cells indicating that the protective effect of D3 was not related to the induction of a metallothionein-like protein in ROS 17 2.8 cells. In the presence or absence of D3, cadmium inhibited osteoblastic function at concentrations below the whole-organ concentration of cadmium in bone as reported in experimental and clinical cadmium-induced osteotoxicity. The extreme sensitivity of ROS 17 2.8 cells to cadmium may relate to the absence of metallothionein synthesis. © 1990.