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⁺

Abstract

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.

Cell death affected by dental alloys: Modes and mechanisms

“…Nonetheless, in 72 h, the early apoptotic rate and Caspase mRNA level of the Pdbased group were both higher than those of the negative groups (p<0.05). This is probably a consequence of copper in Pd-based alloy, which has been reported to be the cause of cell apoptosis 19) . Regarding the CP-Ti alloy, the early apoptotic rate was significantly higher than that of the negative group and so as the activation of Caspase 9 and Caspase 3 mRNA.…”

T-type Ca2+ channels in mouse embryonic stem cells: modulation during cell cycle and contribution to self-renewal

“…On the other hand, increase in sub-G1 fractions at 150 and 300 M Ni 2ϩ could be indicative of apoptotic cell death, an event also associated to blastocyst development and LIF withdrawal-induced mouse ES cell differentiation (10,15,33,39). Alternatively, apoptosis could be caused by toxicity induced by Ni 2ϩ exposure (6). It is important to note that the differentiation effect induced by Ni 2ϩ was only clearly observed at concentrations an order of magnitude higher than those required to selectively block recombinant Ca v 3.2 channels (IC 50 ϳ5-10 M) (21).…”

New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk

“…Caicedo et al (2008), De Boeck et al (1998), Hartwig et al (1990Hartwig et al ( , 1991 and Ponti et al (2009) all reported induction of DNA damage by cobalt chloride in human Jurkat cells by the neutral comet assay, in isolated human lymphocytes using the alkaline comet assay, in HeLa cells by nucleoid sedimentation in sucrose density gradients, and in Balb/3T3 cells by the comet assay, respectively. De Boeck et al (1998) and Van Goethem et al (1997) also reported induction of direct DNA damage with low concentrations of ultrafine cobalt metal in human leukocytes and blood lymphocytes from three different donors using the alkaline version of the comet assay, although in a later paper, De Boeck et al (2003a) were unable to reproduce the DNA damage responses.…”