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.

In July 1979, the Faculty of Pharmacy of the University of Bologna received a proposal from Professor Breccia to hold an International Conference on "Nitroimidazoles: Chemistry, Pharmacology and Clinical Application." Because of the great interest in these drugs in various fields, I was very pleased to accept the proposal and to give the conference the sponsorship of the University of Bologna. It was an added pleasure to accept the chairmanship of the meeting, together with Professors Sensi and Adams. At the same time, the Minister of Education approved a proposal which also came from the Faculty of Pharmacy, to offer an advanced course on the topic "Radiosensitizers of Hypoxic Cells This course was subsequently approved by a special Committee of the NATO Scientific Programme as an Advanced Study Institute. Since the subject matter of both the conference and the course are closely inter-related, it was logical to plan the conference as part of the overall course. Bringing together specialists from quite different and apparently unrelated fields of research, but all with an interest in the study and application of one single group of drugs, is a novel idea with intriguing possibilities. The volumes of the proceedings include contributions from experts with such diverse interests as synthetic chemistry, mechanism of drug action, parasitology, anaerobic bacteria and protozoa, pharmacology and toxicology, radiation sensitizers for use in radiotherapy, and the development of drugs for use in cancer in general.

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 ...

In July 1979, the Faculty of Pharmacy of the University of Bologna received a proposal from Professor Breccia to hold an International Conference on "Nitroimidazoles: Chemistry, Pharmacology and Clinical Application." Because of the great interest in these drugs in various fields, I was very pleased to accept the proposal and to give to the Conference, the sponsorship of the University of Bologna. It was an added pleasure to accept the chairmanship of the meeting, together with Professors Sensi and Adams. At the same time, the Minister of Education approved the proposal also from the Faculty of Pharmacy, to offer an advanced Course on the tOpic: "Radiosensitizers of Hypoxic Cells." This Course was subsequently approved by a special Committee of the NATO Scientific Programme as an Advanced Study Institute. Since the subject matter of both the Conference and the Course are closely inter-related, it was logical to plan the Conference as part of the overall Course. Bringing together specialists from quite different and apparently unrelated fields of research, but all with an interest in the study and application of one single group of drugs, is a novel idea with intriguing possibilities. The volumes of the proceedings include contributions from experts with such diverse interests as synthetic chemistry, mechanism of drug action, parasitology, anaerobic bacteria and protozoa, pharmacology and toxicology, radiation sensitizers for use in radiotherapy and the development of drugs for use in cancer chemotherapy generally.