Metabolism and excretion of (/sup 3/H)misonidazole by hypoxic rate liver

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

OSTI ID:6500306

Smith, B R; Born, J L

This investigation was initiated to determine if misonidazole's biological activity is related to hypoxia-dependent, reductive biotransformation to form reactive metabolites. This study was facilitated by the synthesis of (/sup 3/H)misonidazole and by use of the isolated perfused rat liver as a model system for hypoxic tissue. Reductive metabolism of MISO by perfused livers was enhanced by hypoxic conditions. Formation of a MISO-derived glutathione conjugate (MISO-GSH) and covalent binding of MISO-derived radioactivity to tissue protein was also enhanced by hypoxia. Depletion of hepatic GSH with diethyl maleate increased the extent of covalent binding to protein under both aerobic and hypoxic conditions, and greatly diminished the formation of MISO-GSH. These results support the hypothesis that hypoxic conditions facilitate reductive metabolism of MISO to an alkylating agent, and that GSH plays an intervening role in the alkylation reaction.

• Research Organization: Univ. of New Mexico, Albuquerque
• OSTI ID: 6500306
• Report Number(s): CONF-8311204-
• Conference Information: Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Journal Volume: 10:8
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
BODY
CHEMICAL REACTIONS
CHROMATOGRAPHY
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
EXCRETION
GLANDS
GLUTATHIONE
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
METABOLISM
MISONIDAZOLE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDES
PERFUSED TISSUES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RATS
REDUCTION
RODENTS
SEPARATION PROCESSES
TISSUES
TRITIUM COMPOUNDS
VERTEBRATES