The genotoxicity of physiological concentrations of chromium (Cr(III) and Cr(VI)) and cobalt (Co(II)): an in vitro study.
Humans are exposed to chromium and cobalt in industry, from the environment and after joint replacement surgery from the CoCr alloy in the implant. In this study we have investigated whether Cr(III), Cr(VI), Co(II) and Cr in combination with Co could induce chromosome aberrations in human fibroblasts in vitro at the same concentrations that have been found in the peripheral blood of exposed humans. We used 24 colour M-FISH as a sensitive way to detect translocations and aneuploidy and examined the effects of a 24-h exposure and its consequences up to 30 days after the exposure in order to record genomic instability and/or repair. At these physiological doses the metals induced predominantly numerical rather than structural aberrations. Co was the least reactive and Cr(VI) especially in combination with Co the most. All metals at the highest physiological doses caused simple (gain or loss of 3 or less chromosomes) and complex (more than 49 chromosomes) aneuploidy. All metals at the lowest physiological dose caused a significant increase of total aberrations. Cr(VI) was much more effective than Cr(III) in causing chromosome fragments, which were only induced at the highest doses. There was a slow resolution of aneuploidy with time after exposure. This involved a reduction in the proportion of aneuploid cells and a reduction of the number of chromosomes within cells showing complex aneuploidy. We conclude that these metal ions can cause chromosome aberrations at physiological concentrations and that their main effect is aneugenic.
Bristol Implant Research Centre, Avon Orthopaedic Centre, Southmead Hospital, Bristol BS10 5NB, UK.
Martin
M
Figgitt
Roger
R
Newson
Ian J
IJ
Leslie
John
J
Fisher
Eileen
E
Ingham
Charles P
CP
Case
D024422:Aneugens / Q000633:toxicity*; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D002869:Chromosome Aberrations; D003035:Cobalt / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts; D042822:Genomic Instability; D006801:Humans
D024422:Aneugens; D002857:Chromium; D003035:Cobalt