Effect of hypoxic cell radiosensitizers on glutathione level and related enzyme activities in isolated rat hepatocytes.

  title={Effect of hypoxic cell radiosensitizers on glutathione level and related enzyme activities in isolated rat hepatocytes.},
  author={K. Noguchi and T. Hattori and T. Igarashi and K. Ueno and T. Satoh and H. Kitagawa and H. Hori and T. Shibata and S. Inayama},
  journal={Life sciences},
  volume={37 7},
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-dinitroimidazole-1-ethanol (DNIE); after incubation for only 15 min, GSH was hardly detected. DNIE-mediated GSH loss was dependent upon its concentration… Expand


The use of drugs which deplete intracellular glutathione in hypoxic cell radiosensitization.
Analysis of DNA damage by the alkaline elution assay indicates that DEM enhances radiation-induced single-strand breaks, but does not significantly affect repair, while diamide and N-ethylmaleimide inhibit repair, in addition to enhancing radiation- induced single- Strand breaks. Expand
Non-protein thiols and cellular response to drugs and radiation.
These studies strongly suggest that potential new sensitizers be routinely examined for their capacity to react spontaneously with GSH or to remove cellular NPSH under aerobic as well as anaerobic conditions, especially true for radiosensitizing drugs showing anomalous behavior. Expand
Protective role of the glutathione redox cycle against adriamycin-mediated toxicity in isolated hepatocytes.
Incubation of isolated rat hepatocytes with 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) resulted in the selective and extensive inactivation of glutathione reductase, which resulted in a significant amount of protection from ADR-mediated damage. Expand
Survival curves of irradiated glutathione-deficient human fibroblasts: indication of a reduced enhancement of radiosensitivity by oxygen and misonidazole.
It is suggested that intracellular GSH plays an essential protective role in hypoxia, its effect is reduced in air and practically disappears in 100% oxygen. Expand
Role of glutathione in the hypoxic cell cytotoxicity of misonidazole.
It is reported here that pretreatment of Chinese hamster ovary cells in vitro with diethylmaleate to deplete intracellular glutathione results in a substantial decrease in the shoulder of the survival curve for MIS-treated hypoxic cells, indicating that the cytotoxicity of MIS is not simply a reflection of massive binding of MIS metabolites to cellular constituents. Expand
Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine).
The findings support the conclusion that the S-alkyl moiety of the sulfoximine binds at the enzyme site that normally binds the acceptor amino acid and increases in a manner which is parallel to those of the corresponding isosteric accepter amino acid substrates, i.e. glycine, alanine, and alpha-aminobutyrate. Expand
Electron affinic sensitization. V. Radiosensitization of hypoxic bacteria and mammalian cells in vitro by some nitroimidazoles and nitropyrazoles.
One of the two 2-nitroimidazoles, Ro-07-0582, is much more effective than any of the other compounds and shows a large degree of sensitization in the submillimolar range and the maximum enhancement ratio for this sensitizer is independent of the position of the cells in the mitotic cycle. Expand
Inactivation of glutathione reductase by 2-chloroethyl nitrosourea-derived isocyanates.
  • J. Babson, D. J. Reed
  • Chemistry, Medicine
  • Biochemical and biophysical research communications
  • 1978
Several other 2-chloroethyl nitrosoureas were capable of inactivation of not only purified GSSG-reductase, but also the activity of this enzyme in cell-free extracts of murine lymphoma L5178Y ascites tumor cells and murine bone marrow. Expand
The measurement of lipid peroxidation in isolated hepatocytes.
The results obrained indicate that lipid peroxidation is an important even in carbon tetrachloride hepatotoxicity, but that it appears to be only a subsequent event in bromobenzene toxicity, possibly occurring only as a result of glutathione depletion and cell death. Expand
Potential radiosensitizing agents. Dinitroimidazoles.
New compounds of the nitroimidazole series have been synthesized as radiosensitizers which selectively sensitize hypoxic cells to the lethal effect of radiation. The reaction ofExpand