Comparative chronic in vitro toxicity of hexavalent chromium to osteoblasts and monocytes.
There is increasing concern regarding the long-term biological effects of exposure to low concentrations of metal ions, particularly chromium, in patients following implantation of metal-on-metal hip prostheses. To investigate this, we have evaluated the chronic in vitro response to clinically relevant concentrations of chromium VI in osteoblasts and monocytes over a 4-week period in continuous culture. The cell viability, intracellular reduced glutathione content, glutathione reductase activity and expression, and expression of glutamate cysteine ligase were monitored in both cell types. Monocytes were more susceptible to the toxicity of the metal, and at the end of 4 weeks exposure to 0.5 microM Cr VI, the protein content of cultures had declined to 23.4% +/- 1.0% of control cultures. Both cell types demonstrated temporal increases in reduced glutathione levels, glutathione reductase activity, and glutamate cysteine ligase expression. Only osteoblasts showed a transcriptional increase in reductase expression. Data suggest that both cell types mount an adaptive response to chronic exposure to Cr VI, but this is more potent in osteoblasts, and results in the relative resilience of this cell type to the effects of Cr VI on cell viability.
Raghunathan
Vijay Krishna
VK
Bioengineering Unit, Wolfson Centre, University of Strathclyde, Glasgow, Scotland.
Tettey
Justice N A
JN
Ellis
Elizabeth M
EM
Grant
M Helen
MH
D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006622:Hip Prosthesis / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects*; D011475:Prosthesis Failure; D051381:Rats
D002274:Carcinogens, Environmental; D002857:Chromium; C074702:chromium hexavalent ion; D005980:Glutathione Reductase; D005978:Glutathione