The Effect of L-Buthionine Sulfoximine on the Toxicities and Interactions of As, Cd, Hg and Pb and their Composite Mixture on MCF 7 Cell Line

Abstract

The effect of intracellular level of GSH on the cytotoxicity and interaction of four environmentally relevant metals arsenic, cadmium, mercury and lead (As, Cd, Hg, and Pb) was investigated. L-Buthionine Sulfoximine (LBSO) was used to inhibit the intracellular level of GSH in MCF 7 cells. Both individual and combined cytotoxicities of the four metals on the cells were assayed by spectrofluorometric counting of the surviving cells after 24-hour exposure. Exposure of the cells to three of the studied metals: As, Cd, and Hg resulted in the production of significantly (p<0.5) higher level of cellular GSH relative to the control. However, cells exposed to Pb with or without pretreatment with LBSO exhibited about 50% decrease in cellular GSH. Individual metal toxicity was higher in GSH-depleted cells relative to GSH-rich cells; However, the effect of GSH depletion was slightly metal selective as As and Hg exhibited toxicities. Cells exposed to the composite mixture of all four metals indicated additive and antagonistic interactions in GSH depleted cells and GSH rich respectively.