Uptake and toxic effects of heavy metal ions: interactions among cadmium, copper and zinc in cultured cells.

Absorption of metal ions by KB, HeLa and L-59 cells has been analyzed by atomic absorption spectrophotometry in the course of culture. Ions of the elements of the fourth period in the periodic chart such as Fe(II), Cu(II), Zn(II), Mn(II) and Ni(II) were not taken up, but those of the higher periods, such as Cd(II), Pb(II), Hg(II) and Ag(I) were were taken up easily. The uptake behavior by the cultured cells was in accordance with the characteristic features of metals, that metals in the fourth period are essential elements, and most of the elements of the fifth and the sixth periods are non-essential or toxic elements. The initial rate of Cd(II) uptake and the Cd(II) concentration has a sigmoidal relationship. Cd(II) was absorbed homotropically through cell membranes. The uptake of Cd(II) was specifically inhibited by Cu(II), but was affected little by Zn(II). The toxicity of Cd(II) to KB cells was greatly enhanced in the presence of Cu(II). On the contrary, the toxicity of Cd(II) was reduced by the addition of Zn(II) at several concentrations of Cd(II). The toxicity of Cd(II) did not depend on the amount of Cd(II) absorbed in the cells, but was determined by cofactors such as Cu(II). The interaction between Cd(II) and Cu(II) may be important for Itai-itai disease.