Effect of hypoxic cell radiosensitizers on glutathione level and related enzyme activities in isolated rat hepatocytes
A comparative study of the effect of misonidazole and novel radiosensitizers on glutathione (GSH) levels and related enzyme activities in isolated rat hepatocytes was performed. Incubation of hepatocytes with 5 mM radiosensitizers led to a decrease in the intracellular GSH level. The most pronounced decrease in cellular GSH was evoked by 2,4-dinitromidazole-1-ethanol (DNIE); after incubation for only 15 min, GSH was hardly detected. DNIE-mediated GSH loss was dependent upon its concentration. DNIE reacted with GSH nonenzymatically as well as with diethylmaleate, while misonidazole and 1-methyl-2-methyl-sulfinyl-5-methoxycarbonylimidazole (KIH-3) did not. Addition of partially purified glutathione S-transferase (GST) did not enhance DNIE-mediated GSH loss in a cell-free system. DNIE inhibited glutathione peroxidase (GSH-Px), GST, and glutathione reductase (GSSG-R) activities in hepatocytes, while misonidazole and KIH-3 did not. GSH-Px activity assayed with H/sub 2/O/sub 2/ as substrate was the most inhibited. Inhibition of GSH-Px activity assayed with cumene hydroperoxide as substrate and GST was less than that of GSH-Px assayed with H/sub 2/O/sub 2/ as substrate. GSSG-R activity was decreased by DNIE, but not significantly. Incubation of purified GSH-Px with DNIE resulted in a little change in the activity when assayed with H/sub 2/O/sub 2/ as substrate. 26 references, 2 figures, 4 tables.
- Research Organization:
- Chiba Univ., Japan
- OSTI ID:
- 5438715
- Journal Information:
- Life Sci.; (United States), Vol. 37:7
- Country of Publication:
- United States
- Language:
- English
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GLUTATHIONE
METABOLISM
MISONIDAZOLE
RADIOSENSITIVITY EFFECTS
PEROXIDASES
ENZYME ACTIVITY
TRANSFERASES
COMPARATIVE EVALUATIONS
HYDROGEN PEROXIDE
LIVER CELLS
OXIDOREDUCTASES
PEROXIDES
RATS
SUBSTRATES
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
CARBOXYLIC ACIDS
DRUGS
ENZYMES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IMIDAZOLES
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PORPHYRINS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIZERS
RODENTS
SOMATIC CELLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques