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Genotoxic effects of particles of surgical cobalt chrome alloy on human cells of different age in vitro

Papageorgiou, Iraklis, Yin, Zhirong, Ladon, Dariusz, Baird, Duncan Martin, Lewis, Andrew C., Sood, Aman, Newson, Roger, Learmonth, Ian D. and Case, Charles Patrick 2007. Genotoxic effects of particles of surgical cobalt chrome alloy on human cells of different age in vitro. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 619 (1-2) , pp. 45-58. 10.1016/j.mrfmmm.2007.01.008

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Abstract

Humans are exposed to metals from industry, the environment and from wear debris from worn orthopaedic joint replacements. Patients exposed to worn cobaltchrome hip replacements show an increase of chromosome aberrations in the bone marrow adjacent to the implant and an increase of chromosome translocations and aneuploidy in the peripheral blood. This study has tested whether particles of surgicalcobaltchromealloy are able to induce similar DNA damage and chromosome aberrations in humancells in vitro. Because increasingly young patients are receiving hip replacements it has also tested whether the response is altered at different cellular age in vitro. Primary human fibroblasts, were tested at different pre senescent population doublings (PD10 (young) and PD35 (older)) to particles of cobaltchromealloy for up to 15 days. As in patients there was an increase of aneuploidy, chromosome translocations and DNA damage after exposure to the cobaltchromeparticles in vitro. The overall level of DNA damage and numerical and structural aberrations was approximately the same in young and older cells. However, the cellular reaction to the DNA damage was different. Older cells showed a greater loss of viability and induction of senescence and a lesser rate of mitosis and cell growth than young cells. They showed less change in transcription, particularly of p38 and caspase 10 mRNA levels, than young cells. They showed more complex aneuploidy in association with unseparated or prematurely separated chromatids. This study suggests that at least part of the chromosome changes in patients with worn implants may be due to direct effects of the metal wear particles from the implant. It would be of interest to test whether the altered reaction of the humancells at different in vitroage might correspond with a different incidence of chromosome aberrations in patients at differentages.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: DNA damage; Chromosome aberrations; Age; Aneuploidy; p38
Publisher: Elsevier
ISSN: 0027-5107
Last Modified: 04 Jun 2017 04:20
URI: http://orca.cf.ac.uk/id/eprint/37287

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