Permeability, cytotoxicity, and genotoxicity of Cr(III) complexes and someCr(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(s alen)(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'-ethylen ebis(salicylideneiminato)] have been studied in V79 Chinese hamster lung ce lls. Following exposure of similar to 10(6) cells to 0.4 mM Cr(III) for 4 h , the Cr uptake by single cells was less than 10(-14) g/cell las determined by GFAAS analysis and as confirmed by PIXE analysis where the Cr concentra tion 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 follow ing order: mer-[Cr(glygly)(2)](-) < [Cr(en)(3)](3+) similar to 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+) a t concentrations up to 6 mM. The Cr(III) imine complexes trans-[Cr(salen)(O H2)(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 cell s/mu mol of Cr, respectively. The comparative permeabilities and genotoxici ties of trans-[Cr(salen)(OH2)(2)](+) and [CrO(salen)](+) were similar due t o the instability of the Cr(V) complex at physiological pH values (7.4). Th ere 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 hig hly 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 car cinogen. This has potential implications for the increased use of Cr(III) c omplexes as dietary supplements and highlights the need to consider the gen otoxicities of a variety of Cr(III) complexes when determining the carcinog enic potential of Cr(III) particularly when "high" deliberately administere d doses are concerned.