Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells

Coen, Natasha; Kadhim, Munira; Wright, Esmond; Case, C. P.; Mothersill, Carmel

doi:10.1038/sj.bjc.6600758

Cited by 91 publications

(56 citation statements)

References 43 publications

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“…Macrophage activation caused by titanium particles and increased cell mediator release has been observed in vitro and in vivo [18,19]. In vitro chromosomal damage caused by high concentrations of titanium particles have also been reported [5,6]. Nevertheless, such reactions depend strongly on the applied particle or ion concentration.…”

Section: Discussionmentioning

confidence: 99%

Metal release and corrosion effects of modular neck total hip arthroplasty

Kretzer

Jakubowitz

Krachler

et al. 2009

International Orthopaedics (SICOT)

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Modular neck implants are an attractive treatment tool in total hip replacement. Concerns remain about the mechanical stability and metal ion release caused by the modular connection. Five different implant designs were investigated in an experimental set-up. In vivo conditions were simulated and the long-term titanium release was measured. Finally, the modular connections were inspected for corrosion processes and signs of fretting. No mechanical failure or excessive corrosion could be identified for the implants tested. The titanium releases measured were extremely low compared to in vivo and in vitro studies and were not in a critical range.Résumé Dans les prothèses totales de hanche l'utilisation d'implants avec col modulaire est d'une utilisation fré-quente et pratique. Néanmoins, cette utilisation laisse persister des doutes sur la stabilité mécanique et sur le relargage des ions métalliques. 5 différents implants ont été étudiés en reproduisant les conditions in vivo, en mesurant le relargage de titane et en évaluant la corrosion et les lésions du col. Ce travail n'a pas permis de mettre en évidence d'échec secondaire à une corrosion excessive, et les taux de titane sont restés extrêmement bas dans les limites de l'acceptable.

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Section: Discussionmentioning

confidence: 99%

Metal release and corrosion effects of modular neck total hip arthroplasty

Kretzer

Jakubowitz

Krachler

et al. 2009

International Orthopaedics (SICOT)

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“…Recently, Coen et al (2001Coen et al ( , 2003 have shown that the metal ions, cadmium and nickel, as well as orthopaedic wear debris from a titanium aluminium vanadium alloy hip replacement cause genomic instability. This phenomenon, usually characteristic of radiation exposure (Seymour et al, 1986;Kadhim et al, 1992), resulted in a persistent reduction in clonogenic survival and increase in chromosome aberrations in the distant progeny of cells which appeared to have completely recovered from the exposure.…”

Section: Introductionmentioning

confidence: 99%

Effects of hTERT on metal ion-induced genomic instability

et al. 2006

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There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence is accumulating that the mechanisms can also be triggered by chemicals, especially heavy metals. Humans are exposed to metals, including chromium (Cr) (VI) and vanadium (V) (V), from the environment, industry and surgical implants. Thus, the impact of low-dose stress responses may be larger than expected from individual toxicity projections. In this study, a short (24 h) exposure of human fibroblasts to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic instability in the progeny of exposed cells for at least 30 days after exposure. Acutely, Cr (VI) caused chromatid breaks without aneuploidy while V (V) caused aneuploidy without chromatid breaks. The longerterm genomic instability was similar but depended on hTERT positivity. In telomerase-negative hTERTÀ cells, Cr (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosomes, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with an increased b-galactosidase staining and apoptosis. This instability was not present in telomerasepositive hTERT þ cells. In contrast, in hTERT þ cells the metals caused a persistent induction of tetraploidy, which was not noted in hTERTÀ cells. The growth and survival of both metal-exposed hTERT þ and hTERTÀ cells differed if they were cultured at subconfluent levels or plated out as colonies. Genomic instability is considered to be a driving force towards cancer. This study suggests that the type of genomic instability in human cells may depend critically on whether they are telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse.

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“…The present study results showed that women with the highest tertile of urinary titanium had 47% increased risk of breast cancer, when compared with those with the lowest tertile, although it was not statistically significant. In addition, a previous experimental study has also demonstrated that wear debris from a worn titanium metal produces chromosomal instability (chromatid breaks and minutes), similar to those caused by heavy metals of cadmium and nickel (35).…”

Section: Discussionmentioning

confidence: 93%

Urinary Titanium and Vanadium and Breast Cancer: A Case-Control Study

Tang¹,

Su²,

He³

et al. 2012

Nutrition and Cancer

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Titanium and vanadium are essential trace elements. This study examined the associations of urinary titanium and vanadium with breast cancer risk in a hospital-based case-control study comprising 240 women with incident breast cancer, and 246 cancer-free and age-matched controls who attended health screening assessments in 2 affiliated hospitals of Sun Yat-sen University in Guangzhou between October 2009 and July 2010. Survey data and urine specimens were collected before treatment for the patients and after interview for the controls. The urinary concentrations of titanium and vanadium were measured by inductively coupled plasma mass spectrometry. Women in the second and the highest tertile of vanadium showed 64% and 40% decreased risk of breast cancer, respectively, when compared with those in the lowest tertile after adjustment for established risk factors of breast cancer (ORs [95%CI]: 0.36 [0.21-0.60] and 0.60 [0.37-0.97], respectively). In contrast, urinary titanium was not significantly related to a decreased risk of breast cancer. These results have potentially significant implications on nutritional chemoprevention of breast cancer and the development of new anticancer drugs. Further replications of the study are recommended, and the biological mechanisms warrant clarification.

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Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells

Cited by 91 publications

References 43 publications

Metal release and corrosion effects of modular neck total hip arthroplasty

Metal release and corrosion effects of modular neck total hip arthroplasty

Effects of hTERT on metal ion-induced genomic instability

Urinary Titanium and Vanadium and Breast Cancer: A Case-Control Study

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