Cytotoxicity studies of chromium(III) complexes on human dermal fibroblasts

The cytotoxicity of certain Cr(III) complexes, such as Cr(salen)(H(2)O)(2)](+), Cr(edta)(H(2)O)](-), Cr(en)(3)](3+), Cr(ox)(3)](3-), Cr(pic)(3)], and CrCl(3), which differ in ionic character and ligand environment in human dermal skin fibroblasts, has been studied. After 72 h of exposure to 100 microM doses of chromium(III) complexes, the order in which the complexes had an inhibitory effect on cell viability was Cr(en)(3)](3+) > Cr(salen)(H(2)O)(2)](+) > Cr(ox)(3)](3-) > Cr(edta)(H(2)O)](-) > Cr(pic)(3)] > CrCl(3). Based on viability studies it was confirmed that Cr(en)(3)](3+), a triply charged cation, inhibits cell proliferation, and therefore, it was chosen to carry out further investigations. Cr(en)(3)](3+), at a dose of 50 microM, was found to bring about surface morphological changes, evidenced by cellular blebbing and spike formation accompanied by nuclear damage. TEM analysis revealed substantial intracellular damage to fibroblasts in terms of the formation of apoptotic bodies and chromatin condensation, thus reflecting cell death. FACS analysis further revealed DNA damage by formation of a sub-G(1) peak with 84.2% DNA as aneuploid DNA and arrest of the G(2) / M phase of the cell cycle. Cellular DNA damage was confirmed by agarose gel electrophoresis with the characteristic appearance of a DNA streak in DNA isolated from Cr(en)(3)](3+)-treated fibroblasts. The proposed mechanism suggests the plausible role of Cr(V), formed as a result of oxidation of Cr(III) by cellular oxidative enzymes, in the cytotoxic response. Consequently, any Cr(III) complex that is absorbed by cells and can be oxidized to Cr(V) must be considered a potential carcinogen. This has potential implications for the increased use of Cr(III) complexes as dietary supplements and highlights the need to consider the cytotoxicity and genotoxicity of a variety of Cr(III) complexes and to understand the potential hazards of Cr(III) complexes encountered in research laboratories.