Chromium-Induced Genotoxicity and Interference in Human Lymphoblastoid Cell (TK6) Repair Processes

Abstract

Two model chromium (Cr) compounds, one hexavalent (sodium chromate) and one trivalent (chromium chloride), were investigated in a human lymphoblastoid cell line (TK6) to increase our knowledge regarding Cr-induced genotoxicity mechanisms. Both selected compounds were genotoxic using the comet assay, although the percentage of DNA in tail obtained after treatment with Cr(VI) was significantly higher than that obtained with Cr(III), at the higher concentrations tested. To determine the nature of the induced damage, enzymes recognizing oxidized bases were used. Treatments with formamidopyrimidine (FPG) and endonuclease III (EndoIII) displayed a greater degree of DNA damage, indicating that the induction of oxidized bases accounts for an important proportion of the damage induced by Cr compounds. In addition, the kinetic repair studies showed that generated DNA damage is removed in approximately 8 h, with the damage induced by Cr(III) being removed/repaired more rapidly than damage produced by Cr(VI). To detect Cr interferences with the repair process, a post-treatment was applied after exposure to 2 Gy gamma radiation. Post-treatment significantly delayed the repair kinetics of DNA damage induced by radiation. This interference effect induced by Cr(VI) was more pronounced. In conclusion, evidence indicates that a high proportion of the Cr-induced DNA damage is correlated with oxidative damage, and that both Cr compounds interfere with repair mechanisms involved in repair of DNA damage induced by gamma radiation.

Role of Bacillus subtilis Error Prevention Oxidized Guanine System in Counteracting Hexavalent Chromium-Promoted Oxidative DNA Damage

“…Our results are consistent with a previous study (64) that employed a lymphoblastoid cell line (TK6) treated with Cr(VI), resulting in the generation of oxidative-stress-associated DNA lesions, including 8-oxo-G, which was detected by Fpg on a comet assay. Accordingly, the results of this report confirmed that production of oxidized bases is a mechanism by which Cr(VI) exerts its noxious effects in prokaryotic and eukaryotic cells (64).…”

“…Our results are consistent with a previous study (64) that employed a lymphoblastoid cell line (TK6) treated with Cr(VI), resulting in the generation of oxidative-stress-associated DNA lesions, including 8-oxo-G, which was detected by Fpg on a comet assay. Accordingly, the results of this report confirmed that production of oxidized bases is a mechanism by which Cr(VI) exerts its noxious effects in prokaryotic and eukaryotic cells (64). It has been reported that, in addition to 8-oxo-G, Fpg is also capable of processing 4,6-diamino-5-formamidopyrimidine (FapyAde) or 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), two DNA lesions that are also generated by oxidative stress (65).…”

Cobalt and chromium exposure affects osteoblast function and impairs the mineralization of prosthesis surfaces in vitro

“…19,25 The observed additive effect implies the existence of common downstream mechanisms for the effect of both Co 2þ and Cr 3þ on osteoblast function. Amongst other mechanisms of action, the participation of Co 2þ and Cr 3þ in Fentonlike reactions resulting in oxidative DNA damage, 32,33 and disruption of DNA replication and repair, [34][35][36] may cause the observed additive effects. This is consistent with a study that describes a similar additive effect for iron (Fe 2þ ) and Cr 3þ combination on Fenton-like reaction mediated oxidative DNA damage.…”

Metal in Total Hip Arthroplasty: Wear Particles, Biology, and Diagnosis

“…Additionally, cobalt and chromium inhibit DNA repair and cobalt inhibits topoisomerase II. 47,48 In patients with a metal-on-metal implant, the leukocytes show a significant increase in the number of chromosomal translocations and aneuploidy cells compared with those in patients without a metal-onmetal implant. 49,50 Even at concentrations considered "subtoxic," cobalt and chromium nanoparticles and ions can cause significant DNA damage.…”