Permeability, cytotoxicity, and genotoxicity of chromium (V) and chromium (VI) complexes in V79 Chinese hamster lung cells.
The genotoxicity of Cr(V) complexes in mammalian cells (V79 Chinese hamster lung cells) has been studied for the first time using the in vitro micronucleus assay. Two complexes were investigated, [CrO(ehba)2]-, which undergoes ligand-exchange and disproportionation reactions in the cell growth medium, and [CrO(mampa)]-, which is chemically inert in the medium for the duration of the exposure period. Results of in vitro micronucleus assays show that both complexes are genotoxic and exhibit similar potencies to that of [Cr2O7]2-. The permeabilities of the Cr(V) complexes were also investigated for the first time using particle-induced X-ray emission (PIXE) analysis of individual cells. The Cr uptake increased in the order: [Cr(phen)2-(H2O)2]3+ < [CrO(ehba)2]- < [CrO(mampa)]- < [Cr2O7]2-. Clonal assays showed that Cr(VI) exhibits an expectedly higher cytotoxicity than the Cr(V) complexes. While the genotoxicities of the Cr(V) and Cr(VI) complexes increase according to their permeabilities, the genotoxicities of the Cr(V) complexes are equal to, if not greater than, that of Cr(VI) in terms of the amount of Cr entering the cell. This supports other evidence that Cr(V), produced as a metabolic intermediate from the intracellular reduction of Cr(VI), may be important in Cr-induced cancers.
Dillon
C T
CT
School of Chemistry, University of Sydney, NSW, Australia.
Lay
P A
PA
Bonin
A M
AM
Cholewa
M
M
Legge
G J
GJ
Collins
T J
TJ
Kostka
K L
KL
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D017608:Chromium Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects*; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology; D015162:Micronucleus Tests; D009369:Neoplasms / Q000139:chemically induced; D018675:Toxicity Tests
D002273:Carcinogens; D017608:Chromium Compounds