Permeability, Cytotoxicity, and Genotoxicity of Cr(III) Complexes and Some Cr(V) Analogues in V79 Chinese Hamster Lung Cells

The permeabilities and genotoxicities of the Cr(III) complexes [Cr(en)3]3+, mer-[Cr(glygly)2]-, cis-[Cr(phen)2(OH2)2]3+, and trans-[Cr(salen)(OH2)2]+ and the Cr(V) analogues of cis-[Cr(phen)2(OH2)2]3+ and trans-[Cr(salen)(OH2)2]+ [en being 1,2-ethanediamine, glygly being glycylglycine, phen being 1,10-phenanthroline, and salen being N,N‘-ethylenebis(salicylideneiminato)] have been studied in V79 Chinese hamster lung cells. Following exposure of ∼106 cells to 0.4 mM Cr(III) for 4 h, the Cr uptake by single cells was less than 10-14 g/cell (as determined by GFAAS analysis and as confirmed by PIXE analysis where the Cr concentration was below the limit of detection). Importantly, the Cr(V) analogue of cis-[Cr(phen)2(OH2)2] was significantly more permeable than the Cr(III) complex. The cytotoxicity of the Cr(III) complexes increased in the following order: mer-[Cr(glygly)2]- < [Cr(en)3]3+ ∼ cis-[Cr(phen)2(OH2)2]3+ < trans-[Cr(salen)(OH2)2]+. No genotoxic effects were observed following exposure to mer-[Cr(glygly)2]- or [Cr(en)3]3+ at concentrations up to 6 mM. The Cr(III) imine complexes trans-[Cr(salen)(OH2)2]+ and cis-[Cr(phen)2(OH2)2]3+, which could be oxidized to Cr(V) complexes, induced MN in vitro at rates of 13.6 and 3.3 MN/1000 BN cells/μmol of Cr, respectively. The comparative permeabilities and genotoxicities of trans-[Cr(salen)(OH2)2]+ and [CrO(salen)]+ were similar due to the instability of the Cr(V) complex at physiological pH values (7.4). There was a substantial increase in the permeability of [Cr(O)2(phen)2]+, compared to that of the Cr(III) analogue, which was accompanied by a highly genotoxic response. Consequently, any Cr(III) complex that is absorbed by cells and can be oxidized to Cr(V) must be considered as 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 genotoxicities of a variety of Cr(III) complexes when determining the carcinogenic potential of Cr(III) particularly when “high” deliberately administered doses are concerned.