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Characteristics of Hypoxic Cells that Enhance their Susceptibility
to Chemical Injury.- Prediction and Measurement of Redox Properties
of Drugs and Biomolecules.- Metal-Catalyzed Redox Processes in
Biological Systems and Drug Activation.- Redox Systems Generated by
Electro-chemical Oxidations and Reductions.- The Role of DNA Damage
in the Bioreductive Action of 2-Nitroimidazoles.- Redox Properties
of Radiation Induced Free Radicals.- Reduction of Bleomycin-Fe by
Reductases and Active Oxygen Formation.- Redox Activation of Drugs
by the Red Blood Cell Membrane.- Induction of Stress Proteins and
Drug Resistance by Hypoxia and Applications of Magnetic Resonance
Spectroscopy and Cryospectrophotometry for Detecting Hypoxia in
Tumors.- Mechanisms of Activation of Mitomycin C and AZQ in Aerobic
and Hypoxic Mammalian Cells.- Molecular Interactions and Biological
Effects of the Products of Reduction of Nitroimidazoles.- Redox
Activation of Benzotriazine N-oxides: Mechanisms and Potential as
Anticancer Drugs.- Nitroacridines and Nitroquinolines as
DNA-affinic Hypoxia-selective Cytotoxins.- Metabolic Effects of
Hypoxic Cell Sensitizers.- Does Ro-03-8799 Concentration in Human
Tumour Xenografts Predict Radiosensitization? Comparison with
SR-2508.- Enzyme-directed Bioreductive Drug Development.- Improved
Treatment of Tumours in vivo by Combining the Bioreductive Drug,
RSU-1069, Hydralazine and Hyperthermia.- Assessment of Bioreductive
Drug Toxicity in vitro and in Experimental Tumours in vivo.-
Activity of Bioreductive Agents in Human and Rodent Tumor Cells.-
The Control of Tumour Oxygenation in Mice: The Importance of Tumour
Site.- Critical Events in the Toxicity of Redox Active Drugs.- The
Reductive Activation of Nitroimidazoles; Modification by Oxygen and
other Redox-active Molecules in Cellular Systems.- Fluorescent
Probes for Hypoxia: Chemical Aspects.- Toxicity of Metal Complexes
with Radiosensitizing Properties.- Effects on DNA of Bioreducible
Nitroimidazole and Benzotriazine Drugs.- Response of Repair and
Reduction Deficient Mutants to Agents Requiring Bioreduction.-
Bioreductive Drugs and Radiation: Pharmacokinetics and Clinical
Trials of Etanidazole Radiosensitizer.- The Oncogenic Potential of
Bioreductive Drugs.- Adduct Formation by 2-Nitroimidazole in
Mammalian Cells: Optimization of Markers for Tissue Oxygenation.-
Tumour Blood Flow and its Modulation: Implications for Bioreductive
Drug Activity in vivo.- Poster Presentations.- Participants.
This Workshop, under the auspices of the NATO Advanced Research
Workshop program, was organised to review the current status of
research into redox-activated compounds particularly bioreductive
drugs, and their applications in various fields of medicine, both
as diagnostic and therapeutic agents. The Workshop brought together
key workers in this currently expanding field of research, i.e.
clinici- ans, pharmacologists, biochemists and molecular
scientists. The programme consisted of several sections including
general review lectures, presentations of laboratory-based and
clinical research, some poster presentations and general "round
table" discussions. The topics ranged from oxygen effects in
biological processes, the nature and function of redox proteins
particularly those involved in drug activation, the bioactivation
of drugs used as sensitizers in radiation oncology, novel
approaches to anti-cancer chemotherapy, anti-bacterial agents,
non-steroidal anti-inflammatory drugs, anti-oxidants and varous
clinical applications of chemical modifiers. G.E. ADAMS A. BRECCIA
E.M. FIELDEN P. WARDMAN v ACKNOWLEDGEMENTS The Organisers
gratefully acknowledge the following for their generous financial
support: ARW-NATO Comune di Fermo, Italy Cas sa di Risparmio di
Fermo Istituto di Scienze Chimiche, Bologna, Italy Pharm. Group
ALFA, r,assermann, Schiapparplli, Italy Sadam Indu~tr ie.-' Pharmex
Corp., Bologna, Italy vii CONTENTS Characteristics of Hypoxic Cells
that Enhance their Susceptibility to Chemical Injury ...
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