CADMIUM-INDUCED INHIBITION OF PROLIFERATION AND DIFFERENTIATION OF EMBRYONAL CARCINOMA-CELLS AND MECHANISTIC ASPECTS OF PROTECTION BY ZINC

Murine embryonal carcinoma cells have been used in in vitro models to study the effects of cadmium chloride on proliferation and differentia tion of early embryonic cells. This approach allows the various cell t ypes within the early embryo as well as several developmental mechanis ms to be dissected and studied in isolation using larger numbers of ce lls than would be readily available from the embryo itself. The presen t study shows that both embryonal carcinoma cell proliferation and dif ferentiation into parietal endoderm are inhibited by cadmium chloride. The effects are counteracted by the additional presence of zinc chlor ide. The uptake of cadmium into the cells is inhibited in the presence of zinc chloride, suggesting that competition between these metals fo r passage into the cells contributes to the mechanism underlying the p rotective effect of zinc. In addition, metallothionein gene expression is enhanced more rapidly after simultaneous incubation with zinc chlo ride, indicating that the attenuating effect of zinc on cadmium toxici ty is also partly attributable to detoxification by metallothioneins. (C) 1993 Wiley-Liss, Inc.