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Our previous studies have shown that Cr(III) forms complexes in different cell culture media, whereas Cr(VI) does not form any detectable structure under the same conditions. Because Cr(VI) is known to be more toxic than Cr(III), we hypothesized that the presence of serum proteins in the molecular structure of Cr(III) may be responsible for the difference in toxicity. We investigated the interaction of the Cr(III) complexes with serum proteins and their internalization by U937 macrophage\u2010like cells. By using a proteomic approach, we showed that in the presence of fetal bovine serum, Cr(III) complexes interacted only with albumin, whereas they interacted mainly with albumin, transferrin, and immunoglobulins (Ig) in the presence of human serum (HS). Cr(III) complexes were more easily engulfed by U937 macrophage\u2010like cells when they were formed with HS. To the best of our knowledge, this is the first report on the formation of Cr(III) complexes in the presence of serum proteins and the interaction of these complexes with U937 macrophage\u2010like cells. \u00a9 2010 Wiley Periodicals, Inc. 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