Genotoxic effects of particles of surgical cobalt chrome alloy on human cells of different age in vitro
Humans are exposed to metals from industry, the environment and from wear debris from worn orthopaedic joint replacements. Patients exposed to worn cobalt chrome hip replacements show an increase of chromosome aberrations in the bone marrow adjacent to the implant and an increase of chromosome trans...
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Published in | Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Vol. 619; no. 1-2; pp. 45 - 58 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
01.06.2007
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Subjects | |
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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 cobalt chrome 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 surgical cobalt chrome alloy are able to induce similar DNA damage and chromosome aberrations in human cells 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 cobalt chrome alloy for up to 15 days. As in patients there was an increase of aneuploidy, chromosome translocations and DNA damage after exposure to the cobalt chrome particles 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 human cells at different in vitro age might correspond with a different incidence of chromosome aberrations in patients at different ages. |
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AbstractList | Humans are exposed to metals from industry, the environment and from wear debris from worn orthopaedic joint replacements. Patients exposed to worn cobalt chrome 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 surgical cobalt chrome alloy are able to induce similar DNA damage and chromosome aberrations in human cells 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 cobalt chrome alloy for up to 15 days. As in patients there was an increase of aneuploidy, chromosome translocations and DNA damage after exposure to the cobalt chrome particles 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 human cells at different in vitro age might correspond with a different incidence of chromosome aberrations in patients at different ages. |
Author | Newson, Roger Yin, Zhirong Case, Charles Patrick Learmonth, Ian D Sood, Aman Lewis, Andrew C Ladon, Dariusz Baird, Duncan Papageorgiou, Iraklis |
Author_xml | – sequence: 1 givenname: Iraklis surname: Papageorgiou fullname: Papageorgiou, Iraklis organization: Bristol Implant Research Centre, Avon Orthopaedic Centre, Southmead Hospital, Bristol BS10 5NB, United Kingdom – sequence: 2 givenname: Zhirong surname: Yin fullname: Yin, Zhirong – sequence: 3 givenname: Dariusz surname: Ladon fullname: Ladon, Dariusz – sequence: 4 givenname: Duncan surname: Baird fullname: Baird, Duncan – sequence: 5 givenname: Andrew C surname: Lewis fullname: Lewis, Andrew C – sequence: 6 givenname: Aman surname: Sood fullname: Sood, Aman – sequence: 7 givenname: Roger surname: Newson fullname: Newson, Roger – sequence: 8 givenname: Ian D surname: Learmonth fullname: Learmonth, Ian D – sequence: 9 givenname: Charles Patrick surname: Case fullname: Case, Charles Patrick |
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SubjectTerms | Apoptosis - drug effects Cell Proliferation - drug effects Cell Survival - drug effects Cells, Cultured Cellular Senescence - drug effects Cellular Senescence - genetics Chromium Alloys - toxicity Chromosome Aberrations - chemically induced Chromosome Painting Cytogenetics DNA Damage Gene Expression - drug effects Humans In Vitro Techniques Mitochondria - drug effects Mitochondria - metabolism Mutagens - toxicity Reverse Transcriptase Polymerase Chain Reaction |
Title | Genotoxic effects of particles of surgical cobalt chrome alloy on human cells of different age in vitro |
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