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The Role of Cellular Glutathione in Response of Tumor Cells to Radiation and Drugs

  • Chapter
Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches

Part of the book series: Developments in Oncology ((DION,volume 47))

Abstract

The best known model to explain the observed radiosensit izing actions of oxygen or electron affinic drugs on hypoxic cells irradiated in vitro is that of “radical repair” (1–3). The model states that radiation-induced radicals produced in critical molecules (like DNA) undergo competitive reactions either with oxidizing species, such as oxygen or other electron affinic agents (e.g. misonidazole) leading to damage “fixation” followed by cell death (Figure 1), or with reducing species, such as non-protein thiols (NPSH) leading to damage “repair” (perhaps through hydrogen atom donation) followed by continued cell viability. Support for this model comes from pulse radiolysis techniques. For simple molecules the reactions of molecular oxygen with free radicals occur at essentially diffusion controlled rates, both for radical addition or electron transfer which occurs less frequently (4, 5). The ratio of the rate constant for radical fixation relative to that for repair is in the range of 200–1000; it is constant at about 200 for both poly-U in the presence of GSH and for transforming DNA in solution (6).

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Authors
  1. John E. Biaglow
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  2. Marie E. Varnes
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  3. Edward P. Clark
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  4. Edward R. Epp
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Editors and Affiliations

  1. Wayne State University School of Medicine, Detroit, Michigan, USA

    Frederick A. Valeriote  & Laurence H. Baker  & 

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© 1986 Martinus Nijhoff Publishing, Boston

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Biaglow, J.E., Varnes, M.E., Clark, E.P., Epp, E.R. (1986). The Role of Cellular Glutathione in Response of Tumor Cells to Radiation and Drugs. In: Valeriote, F.A., Baker, L.H. (eds) Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches. Developments in Oncology, vol 47. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2331-0_11

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  • DOI: https://doi.org/10.1007/978-1-4613-2331-0_11

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