Cadmium resistance and content of cadmium-binding protein in two enzyme-deficient mutants of mouse fibroblasts (L-cells)

Abstract

The toxic Cd 2+ ion accumulates in mammalian organisms, the main storage organs are apparently the liver and the kidney. In these organs Cd 2+ is bound to low molecular weight proteins (thioneins) as metallothionein. We describe here the development of resistance to otherwise lethal concentrations of Cd 2+ by two non-epithelial cell lines, both derived from mouse fibroblasts (L-cells). One of the cell lines (clone ID) is deficient in thymidine kinase and resistant to 5-bromodeoxyuridine, the other (A9) deficient in hypoxanthine-guanine phosphoribosyl transferase and resistant to 8-azaguanine. After stepwise increase in Cd 2+ concentration, clone 1D cells had apparently normal growth rate in the presence of 100 micromolar Cd 2+ after 6 months of Cd treatment. The A9 cells were apparently more sensitive to Cd 2+, after about one year's Cd treatment they had apparently normal growth in the presence of 100 micromolar Cd 2+. This concentration of Cd 2+ would kill cells of both cell lines not previously exposed to Cd. In the resistant A9 cells about 40 per cent of the cadmium were bound to a cadmiumbinding protein (Cd-BP) of molecular weight of about 12,000, most probably metallothionein, in the resistant clone 1D cells the corresponding figure was 60 per cent. The non-resistant cell lines had apparently no metallothionein. We have thus found that also non-epithelial cells can synthesize low molecular weight Cd-BP and that there apparently is a good correlation between cadmium resistance and content of Cd-BP.