Heavy metal toxicity following apical and basolateral exposure in the human intestinal cell line Caco-2

Caco-2 is a cell line, derived from a human colon carcinoma, that retains the ability to differentiate in culture into absorptive intestinal cells. Caco-2 cells were used to evaluate the toxicity of three heavy metals-the essential trace elements zinc and copper, and the xenobiotic cadmium. The cells were cultivated on permeable filters until differentiated and were then exposed to the metals either from the apical (luminal) or from the basolateral (serosal) side. Toxicity was measured in dose-effect experiments with reference to cell survival and integrity of the cell monolayer. The metals were more toxic when presented to the basolateral than to the apical cell side. The toxicity ranking was cadmium > > copper > zinc. The cell's ability to transport each metal across the monolayer and the resulting intracellular accumulation could account for the cytotoxic effects. A specific toxic effect observed on a specialized function of these cells was the interference of cadmium in tight-junction integrity as shown by changes in the transepithelial electrical resistance, in the rate of transport of a specific marker across the cell monolayer, and by morphological alterations of the tight junctions.