Orthopaedic cobalt chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition. Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts. The assessment of reproductive risk from maternal exposure to biomaterials, especially those liberated by orthopaedic implants, is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.
Metal-on-Metal (MoM) hip bearings are being implanted in ever-increasing numbers and into ever-younger patients. The consequence of chronic exposure to metal ions is a cause for concern. Therefore, using cytogenetic biomarkers, we investigated a group of patients who have had MoM bearings in situ for in excess of 30 years. Whole blood specimens were obtained from an historical group of patients who have had MoM bearings in situ for in excess of 30 years. Blood was also obtained from an age and sex matched control group and from patients with Metal-on-Polyethylene (MoP) components of the same era. The whole blood was cultured with Pb-Max karyotyping medium and harvested for cytogenetics after 72 hrs. The 24 colour FISH (Fluorescent In Situ Hybridisation) chromosome painting technique was performed on the freshly prepared slides, allowing chromosomal mapping. Each slide was evaluated for chromosomal aberrations (deletions, fragments and translocations) against the normal 46 (22 pairs and two sex) chromosomes. At least 20 metaphases per sample were scored and the number of aberrations per cell calculated.Purpose
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