The protective effect of reduced glutathione oncadmium-induced DNA double-strand breaks

摘要

The heavy metal cadmium (Cd) is a classified carcinogen and can cause DNAdouble-strand breaks (DSBs) by oxidative stress. Since intracellular reducedglutathione (GSH) is an antioxidant and has a thiol group with the ability tocombine Cd, GSH is likely to have a protective effect on Cd-induced DSBs. Totest this hypothesis, human fibroblasts (GM00637) were exposed to differentconcentrations of Cd (0, 5, 10, 20, and 40 muM) for 0, 4, 8, 16, and 24 h. gammaH2AX(a biomarker of DSBs) was quantified by the immunofluorescence andintracellular-reduced GSH were detected by a commercial kit. The results showedthat Cd caused a significant increase in DSBs level and decrease in reduced GSHcontent in human fibroblasts in a concentration- and/or exposure time-dependentmanner. N-acetyl-cysteine (NAC, as a precursor of GSH, 1 mM) pretreatmentsignificantly reduced the Cd-induced DSBs, while L-buthionine-sulfoximine(BSO, a depletion agent for GSH, 50 muM) pretreatment significantly increasedDSBs level. These results suggest that GSH play a protective role in Cd-inducedDSBs in human fibroblasts.