Reduction in cellular glutathione by buthionine sulfbximine and sensitization of murine tumor cells resistant to L-phenylalanine mustard

Combined effect of buthionine sulfoximine and cyclophosphamide upon murine tumours and bone marrow

“…In order to get further GSH tumour, a transplantable murine bladder tumour, i they combined DEM (300mgkg-1) with after CYC treatment correlated inversely with GSH iulting in a decrease to 8% of the control contents. Somfai-Relle et al (1984) have also our studies, 5 mmol kg-I of D, L,-BSO was reported that the sensitivity of L1210 leukaemia cells to L-PAM becomes higher with longer BSO treatments (i.e., at lower GSH levels). In our studies, the ERs of BSO treatments were large at high survival levels (i.e., at small CYC doses).…”

DNA cell cycle distribution and glutathione (GSH) content according to circadian stage in bone marrow of cancer patients

“…It is the most abundant intracellular non-protein thiol and the cellular content amounts to 0.5-10 nmol 1' (Meister & Anderson, 1983;Dusre et al, 1989). It has been demonstrated that bone marrow of both animals and healthy humans contain a low level of intracellular GSH as compared to other normal tissues (Somfai-Relle et al, 1984a;Jaeschke & Wendel, 1985;Tsutsui et al, 1986;Lee et al, 1987;Smaaland et al, 1991b), and this may contribute to the reduced tolerance of bone marrow cells towards cytotoxic drugs.…”

Intracellular Glutathione Content in Leukemias

“…In some studies, tumor GSH content was found to be an important marker to determine the resistance to some chemotherapeutic agents [16][17][18][19], but in others, GSH was not valid for drug resistance [18,20]. Pharmacologic modulation of cellular GSH content (with BSO and cys teine depletion) may change the sensitivity to cytotoxic agents, and tumors may become sensitive to drugs [2,7,8,[21][22][23][24][25][26]. But in other studies, GSH depletion did not change the sensitivity of the tumors [27][28][29].…”

“…It has been shown that intracellular GSH levels may affect the response of cells to chemotherapeu tic agents and radiation. Cells can be sensitized to chemotherapeutics by decreasing intracellular GSH with buthionine sulfoximine (BSO) which is a metabolic inhibitor of y-glutamyl cysteine synthetase [6][7][8]. Drugs which modulate the GSH level and glutatione peroxidase activi ty may play an important role in increasing host survival [9].…”