Modulation of the clastogenic activity of bleomycin by reduced-glutathione, glutathione-ester and buthionine sulphoximine.
In this study an attempt has been made to establish a relationship between bleomycin (BLM)-induced DNA damage and buthionine sulphoximine (BSO)-mediated modified endogenous glutathione (GSH) status in normal human lymphocytes. Present results demonstrate that depletion of endogenous GSH by BSO reduced the clastogenic action of BLM, whereas elevation of endogenous GSH by treating the cells with GSH and GSH-ester, potentiates the cytotoxicity of BLM. A significant reduction in the frequency of deletions and chromatid breaks was observed when BSO-treated cells were treated with BLM. Again the frequency of these two types of aberrations 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 failure of reactivation of the oxidized BLM by reducing agent GSH which is present endogenously. Similarly, it appears that radicals which are generated due to reduction of oxidized BLM by the increased level of cellular GSH, after treating the cells with GSH or GSH-ester, could be responsible for the increasing frequency of deletion and chromatid breaks.
Chattopadhyay
A
A
Department of Zoology, North-Eastern Hill University, Mawlai, Shillong, India.
Choudhury
S
S
Chatterjee
A
A
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002869:Chromosome Aberrations; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D009153:Mutagens; D001761:Bleomycin; D019328:Buthionine Sulfoximine; C042431:S-ethyl glutathione; D005978:Glutathione