Depletion of glutathione in vivo as a method of improving the therapeutic ratio of misonidazole and SR 2508. [BSO; DEM]

Journal Article · Wed Aug 01 04:00:00 EDT 1984 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(84)90330-4· OSTI ID:6407785

Yu, N Y; Brown, J M

Depletion of intracellular glutathione (GSH) can enhance misonidazole (MISO) radiosensitizing efficacy both in vivo and in vitro. However, such treatments may also enhance the systemic toxicity in animals. The purpose of the present study was to test various ways of depleting GSH levels in a variety of experimental mouse tumors, to measure the improvement in the efficacy of MISO and its less toxic analog SR 2508 by this depletion, and to determine the effect of daily GSH depletion on the toxicity MISO and SR 2508. GSH levels were measured daily for 5 days in tumors, livers and brains of mice injected daily with buthionine sulfoximine (BSO), with or without diethylmaleate (DEM). Daily doses of BSO depleted tumor levels of GSH to 20 to 40% of controls by 6 hr after each injection. Injection of DEM 6 hr after BSO further enhanced the depletion. Administration of MISO or SR 2508 at the time of maximum GSH depletion enhanced the MISO efficacy by factors of 2.6 to 8 for depletion to 8% of controls by BSO + DEM, but no enhancement of SR 2508 was seen with tumors at 20% GSH levels achieved with BSO alone in the preliminary experiment. The chronic toxicity of MISO was enhanced not at all or by a factor of up to 2 for BSO and BSO + DEM respectively.

• Research Organization: Stanford Univ. Medical School, CA
• OSTI ID: 6407785
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 10:8; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMISTRY
BODY
BRAIN
CARBOXYLIC ACIDS
CELL KILLING
CENTRAL NERVOUS SYSTEM
CHEMISTRY
DICARBOXYLIC ACIDS
DIGESTIVE SYSTEM
DRUGS
EXPERIMENTAL NEOPLASMS
GLANDS
GLUTATHIONE
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IMINES
IN VIVO
LIVER
MALEIC ACID
MAMMALS
MICE
MISONIDAZOLE
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOINDUCTION
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
VERTEBRATES