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Gold sodium thiomalate toxicity in cadmium-sensitive and cadmium-resistant Chinese hamster ovary cells
M A Nedelman1, R C Elder, K Tepperman
1Department of Biological Sciences, University of Cincinnati, Ohio 45221.
Abstract:
Gold sodium thiomalate was incubated with one cadmium-sensitive cell line and two cadmium-resistant variants. The resistant lines have been reported to synthesize metallothionein (MT) in response to both cadmium and zinc, whereas the sensitive line does not. All cell lines showed a dose-dependent inhibition of growth as a result of gold sodium thiomalate treatment. However, daily comparisons of cell numbers indicate that the cadmium-resistant lines actually increase in number at the highest gold concentrations, whereas numbers of cells in the nonresistant line decrease. MT biosynthesis was measured by monitoring the incorporation of [35S )cysteine into low molecular weight protein. None of the cells synthesized MT in response to gold. When incubated with both zinc and gold, MT was synthesized by both of the cadmium resistant lines; however, the amount of MT synthesized was reduced in the presence of gold which appears to inhibit the uptake of [35S]cysteine by all the cell lines. Although MT is synthesized in the presence of zinc and gold sodium thiomalate, the MT does not have a significant effect on the ability of these cells to withstand high concentrations of gold.
Insights
Gold sodium thiomalate inhibits cell growth, but cadmium-resistant cells increase in number at high gold concentrations. Metallothionein (MT) synthesis is not induced by gold alone, and MT does not significantly enhance cellular resistance to gold.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Metallothionein (MT) is a protein involved in heavy metal detoxification.
- Cadmium-resistant cell lines are known to synthesize MT in response to cadmium and zinc.
- The effect of gold sodium thiomalate on MT synthesis and cellular resistance is not fully understood.
Purpose of the Study:
- To investigate the effect of gold sodium thiomalate on cell growth and metallothionein (MT) synthesis in cadmium-sensitive and cadmium-resistant cell lines.
- To determine if MT plays a role in cellular resistance to gold sodium thiomalate.
Main Methods:
- Incubation of cell lines with varying concentrations of gold sodium thiomalate.
- Monitoring cell proliferation and counting cell numbers.
- Measuring MT biosynthesis via [35S]cysteine incorporation into low molecular weight proteins.
Main Results:
- Gold sodium thiomalate caused dose-dependent growth inhibition in all cell lines.
- Cadmium-resistant cell lines showed increased cell numbers at high gold concentrations, unlike the sensitive line.
- MT was not synthesized in response to gold alone but was produced in the presence of zinc and gold, albeit at reduced levels.
- Gold appeared to inhibit [35S]cysteine uptake in all cell lines.
- Synthesized MT did not significantly enhance cellular resistance to high gold concentrations.
Conclusions:
- Cadmium resistance mechanisms may confer a degree of tolerance to gold sodium thiomalate.
- Metallothionein synthesis is not a primary protective mechanism against gold sodium thiomalate toxicity.
- Gold sodium thiomalate may interfere with cellular processes beyond MT induction, such as nutrient uptake.