DMT1 gene expression and cadmium absorption in human absorptive enterocytes

Divalent metal transporter 1 (DMT1) is a transmembrane, proton-coupled meta l ion transporter that is upregulated in the duodenum of iron-deficient rod ents and in hereditary hemochromatosis patients, suggesting that it may con stitute a key factor in the uptake of dietary iron. Functional expression s tudies in Xenopus oocytes have shown that DMT1 not only mediates transport of iron but also other divalent metal ions, including the toxic metal cadmi um. In the present study, the correlation between the cadmium absorption pr ocess and gene expression of DMT1 was investigated in an experimental model of human absorptive enterocytes. Fully differentiated Caco-2 cells were gr own in monolayers and treated with iron supplemented medium or control medi um for 1, 3 or 7 days. At each time point, cadmium transport experiments ac ross the Caco-2 cell monolayers were performed and gene expression of DMT1 measured. Iron treatment for 3 and 7 days resulted in a 50% reduction in th e cadmium uptake and a 75% reduction in the transport of the metal across t he basolateral membrane. No effects were observed at 24 h. Gene expression of DMT1 in the iron-treated Caco-2 cells was reduced by about 50% at 3 and 7 days and thus, correlated well with the uptake of cadmium. In summary, ou r results indicate that the uptake of cadmium into human absorptive enteroc ytes may be mediated by DMT1. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.