Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine

Stephen X. Skapek, Adrian F. VanDellen, Daniel P. McMahon, Douglas G. Postels, Owen W. Griffith, Darell D. Bigner, Henry S. Friedman

Research output: Contribution to journalArticle

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Abstract

Melphalan-induced toxicity in nude mice following pretreatment with a regimen of L-buthionine sulfoximine (BSO), previously shown to enhance the activity of this alkylating agent against rhabdomyosarcoma and glioma xenografts, was examined. Mice were pretreated with i.p. BSO (2.5 mmol/kg×7 doses at 12-h intervals plus concomitant availability of a 20-m m solution in the drinking water) or vehicle prior to a single i.p. injection of melphalan (35.65 mg/m2). As compared with control animals who received no BSO pretreatment, mice pretreated with BSO lost weight prior to therapy with melphalan (6.9% weight loss vs 0.3% weight gain;P<0.005) and showed a greater mean nadir weight loss after melphalan (3.8% vs 2.1%;P=0.049). Treatment with melphalan was associated with histologic evidence of reversible gastrointestinal toxicity, reversible myelosup-pression, and histologic evidence of acute renal tubular necrosis, with no differences being observed between mice that had been pretreated with BSO and those that had been pretreated with vehicle. No evidence of cardiac, hepatic, or skeletal muscle toxicity was found in melphalan-treated animals. These results suggest that treatment of nude mice with melphalan following BSO-mediated depletion of glutathione does not result in enhanced organ toxicity despite an increase in the antineoplastic activity of this alkylating agent.

Original languageEnglish (US)
Pages (from-to)15-21
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume28
Issue number1
DOIs
StatePublished - Jan 1991

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Buthionine Sulfoximine
Melphalan
Nude Mice
Toxicity
Alkylating Agents
Alkylating Antineoplastic Agents
Weight Loss
Animals
Rhabdomyosarcoma
Heterografts
Glioma
Drinking Water
Antineoplastic Agents
Weight Gain
Glutathione
Muscle
Myocardium
Skeletal Muscle
Necrosis
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Skapek, S. X., VanDellen, A. F., McMahon, D. P., Postels, D. G., Griffith, O. W., Bigner, D. D., & Friedman, H. S. (1991). Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine. Cancer Chemotherapy and Pharmacology, 28(1), 15-21. https://doi.org/10.1007/BF00684950

Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine. / Skapek, Stephen X.; VanDellen, Adrian F.; McMahon, Daniel P.; Postels, Douglas G.; Griffith, Owen W.; Bigner, Darell D.; Friedman, Henry S.

In: Cancer Chemotherapy and Pharmacology, Vol. 28, No. 1, 01.1991, p. 15-21.

Research output: Contribution to journalArticle

Skapek, SX, VanDellen, AF, McMahon, DP, Postels, DG, Griffith, OW, Bigner, DD & Friedman, HS 1991, 'Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine', Cancer Chemotherapy and Pharmacology, vol. 28, no. 1, pp. 15-21. https://doi.org/10.1007/BF00684950
Skapek, Stephen X. ; VanDellen, Adrian F. ; McMahon, Daniel P. ; Postels, Douglas G. ; Griffith, Owen W. ; Bigner, Darell D. ; Friedman, Henry S. / Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine. In: Cancer Chemotherapy and Pharmacology. 1991 ; Vol. 28, No. 1. pp. 15-21.
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