Combined effect of buthionine sulfoximine and cyclophosphamide upon murine tumours and bone marrow.
Two and four treatments of 5 mmol kg-1 of buthionine sulfoximine (BSO) at an interval of 12 h depleted the glutathione (GSH) content in NFSa tumours of C3H/He mice, respectively, to 24.0 and 1.78 percent of the untreated controls. BSO pre-treatments every 12 h enhanced the cytotoxicity of cyclophosphamide (CYC) towards artificial lung micrometastases of NFSa tumours giving enhancement ratios (ERs) ranging from 1.75 to 1.83 and from 2.41 to 2.73, for two and four BSO pretreatments respectively. Large ERs were obtained at low CYC doses (high cell survival). Four BSO pre-treatments at an interval of 12 h did not increase the cytotoxicity of CYC to bone marrow stem cells. Our results suggest a clinical applicability of the combination of BSO and CYC.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D019328:Buthionine Sulfoximine; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D003520:Cyclophosphamide; D005978:Glutathione; D003545:Cysteine