Effect of glutathione on sister-chromatid exchanges in normal and buthionine sulfoximine-treated mice

Based on their ability to induce sister-chromatid exchanges (SCEs) it is evident that thiol-containing radioprotectors can induce DNA damage. However, there were contradictory findings when reduced glutathione (GSH) was tested using two cell lines. The present study demonstrated that GSH can induce SCEs and also delay in cell proliferation in mouse bone marrow cells in vivo. The presence of catalase significantly reduced GSH-induced SCE frequency down to catalase alone levels. An attempt was made to evaluate the effect of GSH treatment in buthionine sulfoximine (BSO)-treated mice (GSH-depleted mice) and the data indicate that induction of SCEs takes place without inducing a delay in cell proliferation or the generation of hydrogen peroxide. Probably, some unknown route is involved by which GSH-degraded product(s) induce SCEs in BSO-treated mice. Therefore, the induction of SCEs by GSH in normal mice may be largely due to hydrogen peroxide generation; however, the involvement of the binding ability of GSH to chromatin and the probable (unknown) route by which GSH-degraded product(s) may cause smaller fraction of SCEs cannot be ruled out.