Toxicity of nickel for mammalian cells in culture.
The effects of nickel chloride were studied in two human cell lines, HeLa and diploid embryonic fibroblasts, as well as in V79 Chinese hamster cells and in L-A mouse fibroblasts. NiCl2 produces a dose-dependent depression of proliferation and mitotic rate. Effects on viability are accompanied by an increasing release of the intracellular enzyme lactic dehydrogenase. Lactic acid production is stimulated. The plating efficiency is reduced, as are DNA and protein synthesis and, to a lesser degree, RNA synthesis. Comparing these results with those of previous studies of the cytotoxicity of other heavy metals in the same test systems, similar effects are observed though with different intensities and slight differences between the cell lines employed. As regards lethal effects (LC50) the following rank order of cytotoxicity can be established: Ni2+ approximately equal to Pb2+ less than Mn2+ less than Hg2+ less than Cd2+; as regards growth inhibition the same rank order is observed as in the case of the LC50 in HeLa and human fibroblasts, but in L-A cells Ni2+ is more inhibitive than the other metal ions listed above with the exception of Cd2+. With respect to colony formation NiCl2 is less effective than PbCl2, MnCl2, and CdCl2. NiCl2 effects in serum-free medium are much faster and more severe than in medium containing serum or serum albumin indicating that serum constituents, notably albumin, bind the metal effectively and inhibit cellular uptake; this confirms reports of other authors on the serum binding and slow uptake of NiCl2. Synchronized cells are most sensitive in the G1 and early S phases of the cell cycle. Together with the finding that thymidine incorporation is affected to a considerable degree this contributes an explanation of the known genotoxic effects of nickel.
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003470:Culture Media; D003864:Depression, Chemical; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008940:Mitotic Index / Q000187:drug effects; D009532:Nickel / Q000633:toxicity*; D012709:Serum Albumin / Q000494:pharmacology
D001798:Blood Proteins; D003470:Culture Media; D012709:Serum Albumin; C022838:nickel chloride; D009532:Nickel