How does chromium and cobalt cause genetic damage?

Metal-ions released from the metal on metal bearing surfaces ofhip protheses are thought to increase chromosomal aberrationsand lead to high levels of DNA damage in patients1 Suchmetal-ions can also induce apoptosis2. It is not clear whetherthe DNA damage observed in patients is a direct effect of metalions or forms the residue from apoptosis. In case of the former,the genetic damage may have mutagenic consequences but incase of the latter the genetic damage is relatively harmless. Inthis study we tested the hypothesis that cells exposed to metalionswhile inhibiting apoptosis do not show DNA damage.Chinese Hamster Ovary cells were cultured in the presenceof cobalt and chromium ions for 24 and 48 hours, in thepresence and absence of the apoptosis inhibitor Cyclosporin-A(CsA). Damage to the cell’s DNA was determined usingcomet-assay3.Results showed that without the presence of CsA, metal-ionscaused significant genetic damage both at 24 and 48 hours.Significantly less DNA damage was seen in cells treated withmetal-ions in the presence of CsA, compared to those withoutCsA (p¼,0.001).It thus seems that metal ions do not directly cause DNAdamage, but lead to apoptosis, which causes DNA to fragment.Our study therefore suggests that much of the DNA damageseen in patients with metal-on-metal implants1 may have beensecondary damage from apoptotic DNA fragmentation. Theshort time frame of our study may explain why we did notobserve direct DNA damage.