Cr(VI)-induced genotoxicity and cell cycle arrest in human osteoblast cell line MG-63.

Abstract

Occupational environments are major exposure routes to Cr(VI). However, Cr(VI) may also establish in bone tissues by ingestion or through Cr containing orthopaedic prostheses that, due to wear and corrosion, may release metal particles and ions potentially affecting bone tissue. The aim of this work was to evaluate the effects of clinically relevant concentrations of Cr(VI) in human osteoblasts, by integrating genotoxic effects, evaluated by the comet assay and cytokinesis-blocked micronucleus assay (scoring the presence of micronucleus, nucleoplasmic bridges and nuclear division index), with the effects on cell cycle and cell viability. Human osteoblasts MG-63 were in vitro exposed to Cr(VI) at concentrations ranging from 0.1 to 5μm, for 24 and 48hours. Results pointed out to a decrease of cell viability for both time exposures in a time- and dose-dependent manner, which was related to cell cycle arrest and DNA damage. Chromosome abnormalities were also observed. Hence, these data suggest that cells arrested in the cell division with DNA damage may have followed cell death pathways, while some surviving ones still revealed DNA damage at chromosome level indicating abnormal cell division progression. In conclusion, Cr(VI) induced cytotoxic and genotoxic effects in human bone cells at concentrations that could be found in patients with metal-on-metal prostheses. In addition, the early onset of genotoxic damage induced by Cr(VI) at low concentrations after 24hours of cell exposure alert to the relevance of periodic monitoring of patients for genotoxicity diagnosis after implantation of prostheses before clinical symptoms appear.