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The Reduction Activation of Nitroimidazoles; Modification by Oxygen and other Redox-Active Molecules in Cellular Systems

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Selective Activation of Drugs by Redox Processes

Part of the book series: NATO ASI Series ((NSSA,volume 198))

Abstract

The ideal biochemical marker for hypoxic cells1–3 would form adducts with cellular molecules uniformly and irreversibly to various cell types only as a function of oxygen concentration during the drug exposure. Additional useful properties include first, that the adduct formation (binding) be primarily to macromolecules (to allow maximum flexibility with respect to subsequent tissue processing and/or analysis), and secondly that it have some simple functional dependence on drug concentration. Clearly, the oxygen concentration range over which binding changes must be similar to the oxygen-dependent phenomena of interest (e.g. radiation sensitivity which has a half maximal value at about 4 micromolar oxygen4). Finally, the ratio of binding in hypoxia to that in normoxia (‘contrast’) should be as high as possible.

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Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Pennsylvania, Donner II - 3400 Spruce St., Philadelphia, Pennsylvania, 19104, USA

    Cameron J. Koch

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  1. Cameron J. Koch
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Editor information

Editors and Affiliations

  1. MRC Radiobiology Unit, Didcot, Chilton, Oxon., OX11 ORD, UK

    G. E. Adams  & E. M. Fielden  & 

  2. Facoltà di Farmacia, Istituto di Scienze Chimiche, Università Degli Studi di Bologna, 40127, Bologna, Via S. Donato, 15, Italy

    A. Breccia

  3. CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK

    P. Wardman

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© 1990 Springer Science+Business Media New York

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Koch, C.J. (1990). The Reduction Activation of Nitroimidazoles; Modification by Oxygen and other Redox-Active Molecules in Cellular Systems. In: Adams, G.E., Breccia, A., Fielden, E.M., Wardman, P. (eds) Selective Activation of Drugs by Redox Processes. NATO ASI Series, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3768-7_22

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  • DOI: https://doi.org/10.1007/978-1-4615-3768-7_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6679-9

  • Online ISBN: 978-1-4615-3768-7

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