Analysis of metal ion-induced DNA damage, apoptosis, and necrosis in human (Jurkat) T-cells demonstrates Ni2+ and V3+ are more toxic than other metals: Al3+, Be2+, Co2+, Cr3+, Cu2+, Fe3+, Mo5+, Nb5+, Zr2+.
It remains unclear how metal released from implants affects cells of the immune system and, in particular, cells of the adaptive immune system, that is, T-helper lymphocytes. In this study, we investigated the effects of aluminum, chromium, cobalt, copper, iron, molybdenum, nickel, niobium, vanadium, and zirconium ions at concentrations from 0.05 to 5.0 mM on human CD4+ T lymphocytes. The DNA damage, apoptosis, necrosis, and proliferation responses of a human T-helper lymphocyte (Jurkat) cell line were evaluated to test our hypothesis that some metals will preferentially induce genotoxicity (DNA damage). Our results demonstrated that metal ions did not preferentially induce Jurkat T-lymphocyte DNA damage prior to other forms of toxicity, that is, apoptosis and/or direct necrosis. Nickel and vanadium induced the most DNA damage and were the most apoptotic metals tested, inducing >50% caspase-9 positive T cells at 0.05 mM and 0.1 mM concentrations, respectively. Cobalt and niobium were the most toxic metals, inducing <50% viability at approximately 0.5 mM concentrations. Nickel and vanadium were the only metals to induce DNA damage at nearly the same concentrations that induced >50% apoptosis (i.e., <0.05 mM). All the metals tested induced T-cell apoptosis at a lower dose than that required to affect DNA damage or toxicity, implying that soluble metals released from implants may not be preferentially genotoxic to lymphocytes.
Department of Orthopedic Surgery, Rush University Medical Center, 1735 West Harrison MC107, Chicago, Illinois 60612, USA.
Marco
M
Caicedo
Joshua J
JJ
Jacobs
Anand
A
Reddy
Nadim James
NJ
Hallab
D017209:Apoptosis / Q000187:drug effects*; D001826:Body Fluids / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D019169:Jurkat Cells; D008670:Metals / Q000633:toxicity*; D009336:Necrosis; D009532:Nickel / Q000633:toxicity*; D018675:Toxicity Tests; D014639:Vanadium / Q000633:toxicity*
D008670:Metals; D014639:Vanadium; D009532:Nickel