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Selective Activation of Drugs by Redox Processes pp 313–323Cite as

Adduct Formation by 2-Nitroimidazole Drugs in Mammalian Cells: Optimization of Markers for Tissue Oxygenation

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

Abstract

Shortly after the identification of sensitizer-adducts as products of reductive metabolism in hypoxic mammalian cells1,2 their use as markers of tissue oxygenation status was proposed3. Carbon-14 and tritium-labelled misonidazole (MISO) were investigated with cells in vitro 4–7 and with animal tissues8–11 as the prototype hypoxic marker. The binding rates of 2-nitroimidazole drugs to cellular molecules were found to depend upon drug structure6, drug concentration6,7, intracellular oxygenation concentration7,12, temperature6 and cell line13,14. Tritiated-MISO has been administered to 21 cancer patients with metastatic lesions from which 24 tumors were resected and analyzed for the presence of sensitizer-adducts12,15,16.Only 11 of these tumors showed autoradiographic or liquid scintillation counting evidence of sensitizer binding in excess of that expected in oxygenated tissue. The recent withdrawal of MISO from investigational drug use has prompted studies to characterize the binding properties of other potential hypoxic markers, especially those of Etanidazole (ETAN).

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References

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Authors and Affiliations

  1. Radiobiology Research Group, Cross Cancer Institute and Department of Radiology and Diagnostic Imaging, University of Alberta, 11560 University Avenue Edmonton, Canada, T6G 1Z2

    J. D. Chapman, J. Lee & B. E. Meeker

Authors
  1. J. D. Chapman
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  2. J. Lee
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  3. B. E. Meeker
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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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Chapman, J.D., Lee, J., Meeker, B.E. (1990). Adduct Formation by 2-Nitroimidazole Drugs in Mammalian Cells: Optimization of Markers for Tissue Oxygenation. 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_29

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  • DOI: https://doi.org/10.1007/978-1-4615-3768-7_29

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6679-9

  • Online ISBN: 978-1-4615-3768-7

  • eBook Packages: Springer Book Archive

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