INFLUENCE OF BUTHIONINE SULFOXIMINE-MEDIATED GLUTATHIONE DEPLETION ONCLASTOGENIC ACTIVITY OF BLEOMYCIN AND GAMMA-RAYS

The extent of induction of chromosome aberrations (CAs) by bleomycin ( BLM) and gamma-rays has been compared in buthionine sulfoximine (BSO)- mediated reduced glutathione GSH-depleted human peripheral blood lymph ocytes. The rationale for BSO treatment is based on the premise that G SH serves as a major endogenous cellular defence against various xenob iotics and GSH depletion itself may lead to significant sensitizations , Radiation and BLM-induced CAs were scored from Ist cycle metaphases in samples with or without BSO. BSO-treated samples showed higher sens itivity to radiation than the BSO-untreated one, whereas reduction in clastogenic action of BLM was observed in the BSO-treated sample. The frequency of all types of radiation-induced CAs was increased except e xchanges. The reduced effect of BLM in GSH-depleted cells could be exp lained on the basis of failure of reactivation of the oxidized BLM by endogenous GSH whereas increased effect of radiation in GSH-depleted c ells could be due to more free-radical induced DNA lesions, less DNA-s hielding effect and low efficient repair.