Mutation Research/Genetic Toxicology and Environmental Mutagenesis

One of the biggest problems with orthopaedic joint replacements has been the tendency for metalon-polyethylene implants to produce particulate wear debris. These particles stimulated adjacent macrophage infiltration, which caused destruction of bone and soft tissue, resulting in aseptic loosening of the implant. This problem led to the development of new implants with articulating surfaces that produce less volumetric wear (metal-on-metal, MOM, and ceramic-on-ceramic, COC). To determine whether there could be adverse biological effects from exposure to particulate wear debris after total hip replacement (THR), we investigated the in vitro genotoxic effects of alumina ceramic (Al2O3) particles in comparison with cobalt–chrome metal (CoCr alloy) particles. Primary human fibroblasts were exposed to Al2O3 nanoparticles or CoCr alloy particles (0.1–10 mg/T-75 flask) for 5 days. There were no significant differences in cell viability between control and ceramictreated cells, at all doses and time-points studied. Cells exposed to CoCr alloy particles showed both dose- and time-dependent cytotoxicity. There was a small but significant increase in micronucleated binucleate cells after 24 h of treatment with >1 mg/T-75 flask of alumina particulates compared with controls, although no clear dose–response was observed. The induction of micronuclei was unaffected by the size or shape of the ceramic particles. The increase in micronucleated binucleate cells was much greater after exposure to CoCr particles for 24 h, showing a clear dose–response curve. No increase in gamma-H2AX foci was noted in cells exposed to ceramic particles, in contrast with a significant increase of these foci in cells exposed to CoCr particles at comparable mass/surface doses. Cytogenetic analysis showed that both types of particle caused mainly numerical rather than structural chromosomal aberrations, with a greater number and variation of lesions induced by CoCr particles. In conclusion, our results show that alumina (Al2O3) ceramic particles are only weakly genotoxic to human cells in vitro when compared with metal (CoCr alloy) particles.

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