Cultured Human Cells with A High Content of Metallothionein Show Resistance Against Gold-Chloride

Abstract

Resistance to gold(III)chloride was tested in cultures of human epithelial cells derived from normal skin. Two cell strains were used, a ‘wild type’ (HE) and a substrain, previously made resistant to 100 μmol/l of CdCI₂ (HE₁₀₀), with a high content of the cysteine-rich cytoplasmic protein, metallothionein. Cell growth was studied for a period of 4 days during exposition to gold-chloride (100-400 μmol/1 of HAuCI₄ 4H₂0). Gold-chloride produced a dose-dependent inhibition of cell proliferation of both cell strains. Compared with untreated control cells, however, the percentage survival after 4 days' treatment with 400 μmol/l was only 11 % of HE cells, vis-à-vis 44% of the HE₁₀₀ cells. After 24 hours' exposition to 200 μmol gold-chloride/I, the subcellular distribution of gold was determined by gel-filtration of cytosols, and subsequent analyses for Au by flame atomic absorption spectrophotometry. In the HE₁₀₀ cells 30% of the cytosolic gold co-eluted with the matallothionein. In the HE cells, which do not contain detectable amounts of metallothionein, only traces of gold were found in the corresponding eluate fractions. The total amount of intracellular gold was 15 % higher in HE_1IW than in HE cells. This study renders it probable that the binding of gold to pre-existing metallothionein in HE₁₀₀ cells affords protection against otherwise lethal gold concentrations. The significance of the results is briefly discussed in relation to therapeutic use of gold substances.