MODULATION OF THE CLASTOGENIC ACTIVITY OF BLEOMYCIN BY REDUCED-GLUTATHIONE, GLUTATHIONE-ESTER AND BUTHIONINE SULFOXIMINE

In this study an attempt has been made to establish a relationship bet ween bleomycin (BLM)-induced DNA damage and buthionine sulphoximine (B SO)-mediated modified endogenous glutathione (GSH) status in normal hu man lymphocytes. Present results demonstrate that depletion of endogen ous GSH by BSO reduced the clastogenic action of BLM, whereas elevatio n of endogenous GSH by treating the cells with GSH and GSH-ester, pote ntiates the cytotoxicity of BLM. A significant reduction in the freque ncy of deletions and chromatid breaks was observed when BSO-treated ce lls were treated with BLM. Again the frequency of these two types of a berrations was increased significantly when GSH- and GSH-ester-treated cells were treated with BLM. The observed reduction in the effect of BLM in GSH-depleted cells could be explained on the basis of the failu re of reactivation of the oxidized BLM by reducing agent GSH which is present endogenously. Similarly, it appears that radicals which are ge nerated due to reduction of oxidized BLM by the increased level of cel lular GSH, after treating the cells with GSH or GSH-ester, could be re sponsible for the increasing frequency of deletion and chromatid break s.