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), Journal Name: Life Sci.; (United States) Vol. 37:7; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
CARBOXYLIC ACIDS
COMPARATIVE EVALUATIONS
DRUGS
ENZYME ACTIVITY
ENZYMES
GLUTATHIONE
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
IMIDAZOLES
LIVER CELLS
MAMMALS
METABOLISM
MISONIDAZOLE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDASES
PEROXIDES
POLYPEPTIDES
PORPHYRINS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RATS
RODENTS
SOMATIC CELLS
SUBSTRATES
TRANSFERASES
VERTEBRATES