Advertisement

The Role of Thiols in Response to Radiation and Drugs

  • John E. Biaglow
  • Marie E. Varnes
  • Edward R. Epp
  • Edward P. Clark

Abstract

Glutathione (GSH) has been implicated as the major intracellular nonprotein thiol involved in protecting hypoxic cells against radiation injury (1–10). In contrast, we have demonstrated increased radiosensitivity for GSH-depleted aerobic and hypoxic A549 human lung carcinoma cells (2–5). This parallel increase in radiosensitivity conflicts with the popular interpretation of existing data regarding the effect of GSH depletion on hypoxic sensitivity alone (5). Subsequently, ratios of (hypoxic slope) / (aerobic slope) may be misleading if GSH depletion alters both responses, but by different mechanisms.

Keywords

Radiation Response Buthionine Sulfoximine Peroxide Reduction Diethyl Maleate Tertiary Butyl Alcohol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. E. Biaglow, M. E. Varnes, E. P. Clark, and E. R. Epp, The role of thiols in cellular response to radiation and drugs. Radiat. Res. 95, 437–445 (1983).PubMedCrossRefGoogle Scholar
  2. 2.
    J. E. Biaglow, M. E. Varnes, E. R. Epp, E. P. Clark, and M. Astor, Factors involved in depletion of glutathione from A549 human lung carcinoma cells: Implications for radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 10, 1221–1227 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    J. E. Biaglow, E. P. Clark, E. R. Epp, M. E. Varnes, and J. B. Mitchell, Nonprotein thiols and the radiation response of A549 human lung carcinoma cells. Int. J. Radiat. Biol. 4, 489–495 (1983).CrossRefGoogle Scholar
  4. 4.
    J. E. Biaglow, M. E. Varnes, E. R. Epp, E. P. Clark, and M. Astor, Redox enzymes and thiol radicals. In: Oxygen and Sulfur Radicals in Chemistry and Medicine (M.A.J. Rogers, A. Breccia, and G. Semerano, Eds.). Academic Press, Lo Scarabeo, Bologna, Italy, 1986.Google Scholar
  5. 5.
    J. E. Biaglow, M. E. Varnes, E. P. Clark, and E. R. Epp, The role of cellular glutathione in response of tumor cells to radiation and drugs. In: Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches (F.A. Valeriote and L.H. Baker, Eds.). Martinus Nijhoff Publishing, Boston, 1986.Google Scholar
  6. 6.
    J. E. Biaglow, M. E. Varnes, E. R. Epp, and E. P. Clark, Factors influencing tertiary butylhydroperoxide metabolism. Submitted to J. Biol. Chem. (1987).Google Scholar
  7. 7.
    J. E. Biaglow, M. E. Varnes, J. B. Mitchell, and A. Russo, Role of the hexosemonophosphate shunt in the cellular response to radiation and drugs. Submitted to Cancer Res. (1987).Google Scholar
  8. 8.
    E.A. Bump, N.Y. Yu, and J.M. Brown, Radiosensitization of hypoxic tumor cells by depletion of intracellular glutathione. Science 217, 544–545 (1982).PubMedCrossRefGoogle Scholar
  9. 9.
    J.B. Mitchell, A. Russo, J.E. Biaglow, and S. McPherson, Cellular glutathione depletion by diethyl maleate or buthionine sulfoximine: No effect of glutathione depletion on the oxygen enhancement ratio. Radiat. Res. 96, 422–428 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    E.P. Clark, E.R. Epp, M. Morse-Gaudio, J.E. Biaglow, The role of glutathione in the aerobic radioresponse: I. Sensitization and recovery in the absence of intracellular glutathione. Radiat. Res. 108, 238–250 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    T. Alper and P. Howard-Flanders, The role of oxygen in modifying the radiosensitivity of E.coli B. Nature, 178, 978–979 (1956).PubMedCrossRefGoogle Scholar
  12. 12.
    J.E. Biaglow, M.E. Varnes, S.W. Tuttle, N.L. Oleinick, K. Glazier, E.P. Clark, E.R. Epp, and L. Dethlefsen, The effect of L-buthionine sulfoximine on the aerobic radiation response of A549 human lung carcinomai cells. Int. J. Radiat. Oncl. Biol. Phys. 12, 139–144 (1986).CrossRefGoogle Scholar
  13. 13.
    I. Selkoff and J. Reich (Eds.), Cellular Bioenergetics. Academic Press, New York 1981.Google Scholar
  14. 14.
    J.E. Biaglow, M.E. Varnes, E.R. Epp, E.P. Clark, and K. Held, Role of glutathione in cellular response to drugs and radiation, IVth International Conference on Oxygen Radicals, San Diego, CA. Pergamon Press, New York 1987 (In press).Google Scholar
  15. 15.
    B. Ketterer, D. Meyer, and K. H. Tan, Intracellular factors affecting the formation and repair of lipid and DNA hydroperoxides, IVth International Conference on Oxygen Radicals, San Diego, CA. Pergamon Press, New York 1987 (In press).Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • John E. Biaglow
    • 1
    • 2
  • Marie E. Varnes
    • 1
    • 2
  • Edward R. Epp
    • 3
  • Edward P. Clark
    • 3
  1. 1.University of PennsylvaniaPhiladelphiaUSA
  2. 2.Case Western Reserve UniversityClevelandUSA
  3. 3.Harvard UniversityBostonUSA

Personalised recommendations