In vivo modulation of glutathione by buthionine sulfoximine: effect on marrow response to melphalan

The effect of giving buthionine sulfoximine (BSO), 0.0265 g/mouse (6 mM), at 12 and 6 hr before treatment with melphalan--0.0 mg, 3 mg, 6 mg, and 9 mg/kg, was studied in C3H mice, and was compared with control groups that received normal saline 12 and 6 hr before identical melphalan treatment. BSO treatment resulted in depletion of GSH levels in bone marrow, liver, and muscle to 65, 13, and 41% of control levels, respectively. Hematological toxicity was assessed by measurement of CFU-S survival and peripheral white cell counts. CFU-S survival decreased with increasing doses of melphalan, but no difference was observed with BSO pre-treatment. Likewise, WBC counts following melphalan 9 mg/kg, were similar irrespective of BSO pre-treatment. These data suggest that the marrow toxicity seen with melphalan is not worsened by pre-treatment with BSO and that if tumors can be pre-sensitized with BSO, there may be a clinical role for melphalan/BSO drug combination.