Rat kidney epithelial cell culture for metal toxicity studies

Summary Evaluation of the potential adverse human health effects of low-level chronic exposure to heavy metals is dependent on the basic knowledge of the cellular and molecular toxicology of these metals. The use of various cell culture systems has greatly facilitated our knowledge of the cellular effects. Inasmuch as most of the acute and chronic toxic effects of metals occur primarily on the renal proximal tubules, the development of a rat kidney epithelial cell culture has provided a unique system to study the uptake and mechanism of toxicity of metals and their intracellular binding ligands. In the presence ofd-valine, fibroblast growth was retarded and a primary epithelial monolayer culture was selectively grown from rat kidney cells. A distinct difference in the uptake of chemically similar divalent metals, such as Pb²⁺, Hg²⁺, Cd²⁺, and Zn²⁺, was observed in these cells. Both Pb²⁺ and Hg²⁺ were more avidly taken up by kidney cells than Cd²⁺ and Zn²⁺ salts and they also showed increased toxicity. On the other hand, the cellular uptake of Cd from cadmium-metallothionein (CdMT) was much less than from CdCl₂, but CdMT was about seven times more toxic than CdCl₂ when added to the renal cell culture. The cytotoxicity of CdCl₂ was decreased significantly with pretreatment of the cells with CdCl₂, although this had no effect on the toxicity of CdMT. The cellular toxicity of CdMT occurred probably during the process of its transport across the plasma membrane whereas that of CdCl₂ occurred after it had entered the cell. Thus rat kidney epithelial cells may be a useful tool to study the mechanism of renal toxicity of environmental chemicals and drugs. This work was funded by grants-in-aid of research from the Kidney Foundation of Canada.