Tuesday, September 13, 2011

Reviewing the historical Journal literature for publications discussing Cancer risk associated with joint/hip implants (8 of x)

(this series is looking at articles that began suspecting the relationship between cancer risk and metal on metal hips since 1995.)
Couple of definitions might be in order before you read this abstract:
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer.
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders (birth defects). Some cancer cells also have abnormal numbers of chromosomes.
Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to that of the whole organism. There are a number of theories as to why senescence occurs, including ones that claim it is programmed by gene expression changes and that it is the accumulative damage of biological proces
In mitosis, one cell divides to produce two genetically identical cells
 In genetics, genotoxicity describes a deleterious action on a cell's genetic material affecting its integrity. Genotoxic substances are known to be potentially mutagenic or carcinogenic, specifically those capable of causing genetic mutation and of contributing to the development of tumors
Remember, this study is looking at effects from metal on metal in vitro (isolated lab type experiment) vs in vivo whereby the test is done on the organism in its normal intact state.
Mutat Res. 2007 Jun 1;619(1-2):45-58. Epub 2007 Jan 25.

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


Bristol Implant Research Centre, Avon Orthopaedic Centre, Southmead Hospital, Bristol BS10 5NB, United Kingdom.


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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