Studies on nickel-induced inhibition of fibroblast growth

Nickel chloride inhibited the growth of 3T3 mouse fibroblasts in culture within 72 hr at 100 mum. This cytostatic effect was not accompanied by a loss in cell viability as judged by leakage of lactate dehydrogenase into the culture medium. In the log phase of growth the inhibitory effect of 500 mum nickel chloride was evident within 4 hr of exposure. This was not accompanied by an alteration in cellular reduced glutathione content, indicating that oxidative stress was not occurring in the cells. Inclusion of 100 nm alpha-tocopherol in the culture medium prevented the cytostatic effect of nickel. Pretreatment with 500 mum nickel chloride for 72 hr did not alter glutathione reductase of peroxidase activities. Nickel has been implicated in the toxic reactions occurring in connective tissue following its use in orthopaedic implants. This study shows that the metal inhibits cell growth and may thus depress the ingrowth of connective tissue in vivo around the site of implant. Furthermore, alpha-tocopherol (vitamin E) may be valuable in preventing some of the problems arising from poorly fitted or loose implants in vivo.