title: Macrophages detoxify the genotoxic and cytotoxic effects of surgical cobalt chrome alloy particles but not quartz particles on human cells in vitro.
abstract: Particles of surgical cobalt chrome alloy are cytotoxic and genotoxic to human fibroblasts in vitro. In vivo orthopaedic patients are exposed to cobalt chrome particles as a result of wear of a joint replacement. Many of the wear debris particles that are produced are phagocytosed by macrophages that accumulate at the site of the worn implant and are disseminated to local and distant lymph nodes the liver and the spleen. In this study we have tested whether this process of phagocytosis could have altered the cytotoxic and genotoxic properties of the cobalt chrome particles. Quartz particles have been investigated as a control. Micron-sized particles of cobalt chrome alloy were internalised by either white cells of peripheral blood or by THP-1 monocytes for 1 week and 1 day, respectively. The particles were then extracted and presented at different doses to fibroblasts for 1 day. There was a reduction of the cytotoxicity and genotoxicity of the cobalt chrome particles after phagocytosis by white cells or THP-1 cells. Cobalt chrome particles that were internalised by fibroblasts also showed a reduction of their cytotoxicity but not their genotoxicity. In contrast the cytotoxicity and genotoxicity of quartz particles was increased after internalisation by THP-1 cells. The surface morphology of the cobalt chrome particles but not the quartz particles was changed after phagocytosis by THP-1 cells. This study suggests that the genotoxic and cytotoxic properties of particles that fall within the size range for phagocytosis may be highly complex in vivo and depend on the combination of material type and previous phagocytosis. These results may have relevance for particle exposure from orthopaedic implants and from environmental or industrial pollution.
authors.affiliation: Bristol Implant Research Centre, Avon Orthopaedic Centre, Southmead Hospital, and Department of Chemistry, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: I
authors.initials: I
authors.lastname: Papageorgiou
authors.forename: V
authors.initials: V
authors.lastname: Shadrick
authors.forename: S
authors.initials: S
authors.lastname: Davis
authors.forename: L
authors.initials: L
authors.lastname: Hails
authors.forename: R
authors.initials: R
authors.lastname: Schins
authors.forename: R
authors.initials: R
authors.lastname: Newson
authors.forename: J
authors.initials: J
authors.lastname: Fisher
authors.forename: E
authors.initials: E
authors.lastname: Ingham
authors.forename: C P
authors.initials: CP
authors.lastname: Case
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002858:Chromium Alloys / Q000494:pharmacology*; D020552:Comet Assay; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects* / Q000648:ultrastructure; D010586:Phagocytes / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D011791:Quartz / Q000494:pharmacology*
chemical_list: D002858:Chromium Alloys; D011791:Quartz