Effect of systemic glutathione depletion by buthionine sulfoximine on sensitivity of murine bladder cancer to cytotoxic agents.

Abstract

The effect of systemic glutathione (GSH) depletion on sensitization of bladder cancer cells to various antineoplastic agents was investigated using murine model, MBT-2. Subcutaneous injection(s) of buthionine sulfoximine (BSO) significantly depleted the GSH content in the tumor and organs. BSO pretreatment produced significant enhancement in the antitumor effect of cyclophosphamide (CY), though it failed to sensitize the tumors to doxorubicin hydrochloride (Adriamycin), cisplatin, mitomycin C, JM-8, methotrexate, vinblastine, and tumor necrosis factor. Mice tolerated cytotoxic agents alone and in combination with BSO except for cisplatin in combination with BSO. A 29 percent (4/14) mortality rate was observed in mice treated with BSO and divided schedule of cisplatin.

• Authors: K E Lee, R D Mayer, A T Cockett
• Journal: Urology (Urology) Vol. 34 Issue 6 Pg. 376-80 (Dec 1989) ISSN: 0090-4295 [Print] United States
• PMID: 2595883 (Publication Type: Journal Article)

Chemical References

• Antimetabolites
• Antineoplastic Agents
• Methionine Sulfoximine
• Buthionine Sulfoximine
• Glutathione

Topics

• Animals
• Antimetabolites (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Buthionine Sulfoximine
• Carcinoma, Transitional Cell (drug therapy)
• Female
• Glutathione (analysis, antagonists & inhibitors)
• Kidney (analysis)
• Liver (analysis)
• Lung (analysis)
• Methionine Sulfoximine (administration & dosage, analogs & derivatives)
• Mice
• Mice, Inbred C3H
• Myocardium (analysis)
• Tumor Cells, Cultured
• Urinary Bladder Neoplasms (drug therapy)