Gillette (USA), C.D. Klaassen (USA), J.J. Kocsis, (USA), D.B. Menzel (USA), M. Mercier (Belgium), R.A. Neal (USA), F. Oesch (BRD), S. Orrenius (Sweden), H. Remmer (BRD), M. Roberfroid (Belgium), H. Vainio (Finland) and C.M. Witmer (USA), acting 'as a committee under G.G. Gibson (UK), D.J. Jollow (USA), D.V. Parke (UK) and R. Snyder (USA), co-chairmen, THE SECOND INTERNATIONAL SYMPOSIUM ON BIOLOGICAL REACTIVE INTERMEDIATES was convened at the University of Surrey in the United Kingdom on July 14-17, 1980. This volume derives directly from the presentations at the symposium. The University of Surrey, which is located in Guildford, Surrey, provided a congenial atmosphere for this conference and we would like to take this opportunity to thank the local organizing committee and especially Dr. G. Gordon Gibson, for all their efforts in both scientific and social arrangements. Special thanks are extended also to the graduate students of the Biochemistry Department (especially Ms. Tricia Breacker and Mr. Paul Tamburini) and to the conference secretaries who unstintingly gave of their time in a variety of roles to ensure the smooth functioning of the symposium. We wish to acknowledge the tireless efforts of the distinguished scientists who agreed to chair the sessions of the symposium: A. Hildebrandt (BRD), H. Remmer (BRD), L. Goldberg (USA), S. Orrenius (Sweden), H. Uehleke (BRD), J.R. Gillette (USA), C. Netter (BRD), M. Mercier (Belgium), F. Oesch (BRD), E. Boyland (UK), J.E. Gibson (USA), C.D. Klaassen (USA) and J.W. Gorrod (UK). The mounting of a large scale international symposium is fraught with many impediments, not the least of which are the financial and logistical problems of assembling a group of internationally distinguished scientists in one place at the same time. Success in such endeavors requires concerned and active sponsors. The three sponsoring

Much of organic chemistry is based on the ability of suitably structured chemicals to bind together through the formation of covalent bonds. Biochemistry is replete with exam ples of enzymatically catalyzed reactions in which normal body constituents can be linked through covalent bonds during the process of intermediary metabolism. The finding that xenobiotic chemicals that enter the body from the environment, are metabolized to highly reactive species, and then covalently react with cellular macromolecules to induce toxic and carcinogenic effects was an observation that spawned the research featured in the Fifth International Symposium on Biological Reactive Intermediates (BRI V). The group of investigators that became fascinated with this process and its signifi cance in terms of human health began their discussions in Turku, Finland (J 975), and continued them at Guildford, England (1980), College Park, Maryland (1985), Tucson, Arizona (1990), and Munich, Germany (1995). Among the results were a series of reports listed below, as well as the book for which this serves as the Preface. • Jollow, DJ., Kocsis, J.J., Snyder, R. and Vainio, H. (eds), Biological Reactive Intermediates: Formation, Toxicity and Inactivation, Plenum Press, NY, 1975. • Snyder, R., Park, D.V., Kocsis, J.J., Jollow, D.V., Gibson, G.G. and Witmer, C.M. (eds), Biological Reactive Intermediates II: Chemical Mechanisms and Biological Effects, Plenum Press, N.Y., 1982.

This volume presents a discussion of the biological effects produced following the metabolism of xenobiotic chemicals to chemically reactive metabolites, i.e., toxic and carcinogenic effects, which have been the basis of all five earlier volumes in this series. In particular, this volume devotes sections to structure-activity relationships, recent advances in the understanding of the chemistry of reactive metabolites, and the generation and activity of reactive oxygen species with special emphasis on nitric oxide. There are also segments on DNA damage by reactive metabolites and DNA repair, tissue specific responses to BRIs, and human health effects of BRIs. The papers that comprise this volume were submitted by world class scientists who were in attendance at The Symposium on Biological Reactive Intermediates VI at the Université René Descartes, July 16-20, 2000.