The toxicity of chloride salts of physiological (zinc, manganese, nickel) and non-physiological (cadmium) bivalent metal ions was studied in normal or carcinogen-transformed mouse embryo fibroblast cells. The dose response curves for toxicity to both types of cells exhibited similar shapes. The transformed cells, however, were about twice as sensitive to zinc toxicity as normal cells. When normal and transformed cells were grown together and incubated for several hours with an appropriate concentration of zinc, the malignant cells were selectively killed. Cadmium was much more toxic than the three other metal ions in both types of cells. Its toxic effect was reversed by simultaneous addition of zinc at nontoxic concentrations.
We examined the influence of nontoxic concentrations of each of two essential (Zn++ and Mn++) and one nonessential (Ni++) bivalent metal ions on spontaneous and radiation-induced neoplastic transformation and specific gene mutations in mammalian cells. All three metals induced low levels of transformation in mouse BALB/3T3 cells but exerted no mutagenic effect in CHO cells (hprt locus) over a broad range of concentrations. Continuous incubation for 8 or 15 days with each of the metal ions did not enhance the frequency of cell killing, transformation, or mutations induced by acute exposure to x-rays. Zn++, however, had a small but consistent protective effect on the induction of all three endpoints by x-irradiation.
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