TOXICITY OF HEAVY-METALS IN CULTURED-HEPATOCYTES

The cytotoxicity of three heavy metals that are representative environmental contaminants was investigated in primary cultures of rat hepatocytes. The cells were exposed to Cd, Ag or Hg and to mixtures comprised of Cd and either Ag or Hg at various concentrations. Incorporation of [3H]arginine ([3H]Arg) into proteins was used to monitor cytotoxic effects. In parallel, the uptake of metals by the cells was also determined. Concentration‐response profiles for each individual agent show that among the metals studied Cd is the most cytotoxic. This effect is not due to preferential uptake because the amounts of Ag and Hg accumulated by the cells (at low exposure concentrations) were similar to those of Cd. When Ag was used in combination with Cd, amino acid incorporation data showed no evidence of modulated toxicity. In contrast, when Hg was added with Cd, the results suggested the possibility of interaction: The reduction in incorporated [3H]Arg was more pronounced than that expected on the basis of individual responses. Measurement of metal uptake by the cells revealed that intracellular levels of Ag were comparable whether Cd was present or not. Similarly, the amount of Cd accumulated by the hepatocytes was not significantly affected by the presence of Ag or Hg. In conclusion, the present data describe the cytotoxicity of nonessential heavy metals in hepatocytes and their concomitant accumulation by the cells. It is therefore possible to examine one phenomenon in relation to the other. The results are further discussed in the light of the bioinorganic properties of the metals investigated. Copyright © 1990 SETAC