title: L-buthionine-sulfoximine-mediated radiosensitization in experimental interstitial radiotherapy of intracerebral D-54 MG glioma xenografts in athymic mice.
abstract: An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO)-mediated depletion of tumor glutathione levels. Administration of L-BSO [2.5 mmol/kg intraperitoneal injections x 4 doses plus concomitant availability in acidified (pH 3.0) drinking water at a concentration of 20 mM] resulted in depletion of tumor glutathione levels to 0.15 mumol/g wet weight (7.9% of control). The therapeutic activity of i.c. interstitial radiotherapy with an 125I seed was enhanced after L-BSO-mediated glutathione depletion, with increases in median survival of 13.4 to 30.5% over that seen with 125I seeds alone. These studies demonstrate a potential role for BSO in enhancing the therapeutic activity of interstitial radiotherapy.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina.
authors.forename: B E
authors.initials: BE
authors.lastname: Lippitz
authors.forename: E C
authors.initials: EC
authors.lastname: Halperin
authors.forename: O W
authors.initials: OW
authors.lastname: Griffith
authors.forename: O M
authors.initials: OM
authors.lastname: Colvin
authors.forename: G
authors.initials: G
authors.lastname: Honore
authors.forename: C B
authors.initials: CB
authors.lastname: Ostertag
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000532:radiotherapy*; D019328:Buthionine Sulfoximine; D005910:Glioma / Q000532:radiotherapy*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
chemical_list: D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine