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.

Notes

N. El-Yamani and L. Zúñiga were supported by postgraduate fellowships (PIF) from the Uninversitat Autonoma de Barcelona. E. Stoyanova was supported by a postgraduate fellowship from the Generalitat de Catalunya. This investigation was supported in part by a grant of the Generalitat de Catalunya (2009SGR-725).