PMID: 3744933Jul 1, 1986Paper

Combined radiation-protective and radiation-sensitizing agents. III: Radiosensitization by misonidazole as a function of concentrations of endogenous glutathione or exogenous thiols

International Journal of Radiation Oncology, Biology, Physics
C J KochK A Baer

Abstract

Radiosensitization of V79 Chinese hamster fibroblasts by 0.5 mM misonidazole is a smooth function of endogenous glutathione (GSH) levels as modulated upwards by pre-incubation in medium containing cysteamine, or downwards by pre-incubation in medium containing buthionine sulfoximine. The enhancement ratio (radiation sensitivity in nitrogen/radiation sensitivity in nitrogen +/- sensitizer or thiol) varies from 1.3 at 12 mM to 2.25 at less than 0.1 mM endogenous GSH. The enhanced radiosensitivity of thiol-depleted hypoxic cells is reversed when exogenous thiols are added, and for equivalent ER, the exogenous thiol concentrations are much lower than the endogenous GSH concentrations. Measurement of intracellular drug concentrations amplified rather than diminished the above discrepancy, since intracellular concentrations of cysteamine were lower and glutathione much lower than the extracellular concentrations. Three possible explanations are addressed: an external membrane component of damage is involved, long-range protection to DNA target radicals is possible from outside the cell (e.g., donation of electrons), and (c) endogenous glutathione is not in a free or exchangeable state (e.g., bound).

References

Apr 1, 1985·The British Journal of Radiology·D C Shrieve, J Denekamp
Feb 1, 1983·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·R J Hodgkiss, R W Middleton
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN

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Citations

Jan 1, 1988·Pharmacology & Therapeutics·O Vos, W S Roos-Verhey
Jan 1, 1990·Pharmacology & Therapeutics·X Q ShanD P Jones
Jan 1, 1990·Pharmacology & Therapeutics·E A Bump, J M Brown
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Apr 1, 1989·International Journal of Radiation Oncology, Biology, Physics·C J KochP Hettiaratchi
Jan 1, 1992·International Journal of Radiation Oncology, Biology, Physics·K A Skov, H S MacPhail

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