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Drug metabolism—From microbe to man. A symposium in honour of Richard Tecwyn Williams
Reviews of recent publications-Fd can be obtained in some other way is the scientific one and this requires careful examination of all the evidence. He also concludes that no alternatives to animal experiments for toxicity are compatible with the present safety standards demanded by Parliament, and clearly feels that to concentrate on finding alternatives to experiments that cause pain or distress to animals has the greatest chance of success. The final chapter of the book lists the conclusions and also includes a valuable list of suggestions to all interested bodies. Drug MetaboliswFrom Microbe to Man. A Symposium in Honour of Richard Tecwyn Williams. Edited by D. V. Parke and R. L. Smith. Taylor and Francis Ltd., London, 1977. pp. xii + 460. E25.00. This book consists of a series of 24 research papers presented at a symposium held at the University of Surrey, Guildford, during April 1976. The symposium was held in honour of Professor R. T. Williams, who recently retired from the Chair of Biochemistry at St. Mary’s Hospital Medical School, London. Much of our present knowledge on the metabolism of xenobiotics stems from the pioneering work of Professor Williams and his colleagues, including his publication in 1947 of the first ‘classic’ textbook on the subject entitled Detoxication Mechanisms--The Metabolism of Drugs
and
Allied
Organic
Compounds.
The enzymic processes by which xenobiotics are metabolized in the mammalian liver were broadly divided by Professor Williams into two categories. Phase I biotransformations, involving enzymes of the microsomal cytochrome P-450-dependent mixedfunction oxidase complex, include oxidative, reductive and hydrolytic reactions; the resultant metabolites may be conjugated with various endogenous acceptors by Phase II enzymes. Aspects of both Phase I and Phase II pathways of xenobiotic metabolism were covered by papers presented at the Guildford symposium. For example, the paper on carbon oxidation by D. M. Jerina and J. W. Daly deals with epoxides as intermediates in the aromatic hydroxylation of xenobiotics and with the importance of such arene oxides in the activation of polycyclic hydrocarbons to carcinogens. A paper by A. H. Beckett considers various aspects of the oxidation of nitrogen in foreign compounds, and the factors responsible for the control of xenobioticmetabolizing enzymes are considered by D. V. Parke, Papers by G. J. Dutton and co-workers, by K. S. Dodgson and by P. L. Grover deal with the three important Phase II pathways of conjugation with D-glucuronic acid, sulphate and glutathione. respectively. As the title suggests, this volume aims to cover xenobiotic metabolism in all species, and various papers are devoted to metabolism by man, nonhuman primates, birds, fish. invertebrates, plants and micro-organisms, In addition, aspects of species differences in both Phase I and Phase II reactions are considered in a number of the papers. Pharmacokinetics, pharmacogenetics and the use of cell suspensions and cultures for metabolic studies are also discussed. In general, the papers are essentially review articles II,174 I
Cosrnrr
Toxicol.
Vol. 17. No. 4
401
considering the basic principles of various aspects of the subject, rather than presentations of the authors’ latest research findings. In this respect this volume differs from the series entitled Microsomes and Drug Oxidations reviewed earlier (Cired in F.C.7: 1970, 8, 546; ibid 1975, 13, 270; ibid 1978, 16, 383). Furthermore, the extraction of information from the book under review is greatly assisted by the excellent author and subject indexes. A publication to be recommended. Pathology of Laboratory Animals. Vols I & II. Edited by K. Benirschke, F. M. Garner and T. C. Jones. Springer-Verlag. Berlin, 1978. pp. 2225. DM 565.30 (2 vols). The need for a good textbook on the pathology of laboratory animals was felt several decades ago when experimental pathology and biochemistry were in their infancy. R. Jaffe gallantly responded to this need and in 1931 gathered the information then available into the first textbook of laboratory animal pathology. This remained the only reference book on this topic until 1958 when, together with P. Cohrs and H. Meessen and helped by a large group of collaborators, he produced a much enlarged version of his earlier work. Both of these excellent texts were written in German. Since 1958. some major advances have taken place in pathology and, furthermore, an increasing burden has been imposed on the pathologist by demands from consumers, industry and government agencies for safety assurances. These developments have made the availability of an up-to-date text, preferably written in English, an urgent necessity. An attempt to tackle part of the problem was made some years ago by E. Cotchin and F. J. C. Roe, who, in collecting together a series of articles on rodent pathology, provided considerable help for the harassed pathologist. but they left some important gaps unfilled. The two volumes named above go a long way towards meeting this urgent need. The first, which may be identified as dealing with ‘systematic pathology’, considers the disease processes in the so-called systems common to all mammals (the cardiovascular. nervous and respiratory systems. for example). The material presented is concerned not only with commonly occurring pathological features but also with more esoteric pathology. The latter is particularly important in toxicology, since rare lesions are more likely to be attributed in error to a test chemical than are commonly occurring ones. The second volume of this pair is devoted to special topics. The infective diseases are the most importantamong these, and a succession of contributors deals succinctly with the various disease processes caused by lower organisms, from viruses to protozoa and helminths. Somewhat surprisingly. tumours are included in this volume. Neoplasia is a proliferative disorder, and one of the major problems in pathology is to distinguish it from non-neoplastic proliferative conditions. It would therefore be an advantage il in future editions, the chapter on tumours could be included with the systematic pathology where conditions associated with non-neoplastic proliferation are
and
Allied
Organic
Compounds.
The enzymic processes by which xenobiotics are metabolized in the mammalian liver were broadly divided by Professor Williams into two categories. Phase I biotransformations, involving enzymes of the microsomal cytochrome P-450-dependent mixedfunction oxidase complex, include oxidative, reductive and hydrolytic reactions; the resultant metabolites may be conjugated with various endogenous acceptors by Phase II enzymes. Aspects of both Phase I and Phase II pathways of xenobiotic metabolism were covered by papers presented at the Guildford symposium. For example, the paper on carbon oxidation by D. M. Jerina and J. W. Daly deals with epoxides as intermediates in the aromatic hydroxylation of xenobiotics and with the importance of such arene oxides in the activation of polycyclic hydrocarbons to carcinogens. A paper by A. H. Beckett considers various aspects of the oxidation of nitrogen in foreign compounds, and the factors responsible for the control of xenobioticmetabolizing enzymes are considered by D. V. Parke, Papers by G. J. Dutton and co-workers, by K. S. Dodgson and by P. L. Grover deal with the three important Phase II pathways of conjugation with D-glucuronic acid, sulphate and glutathione. respectively. As the title suggests, this volume aims to cover xenobiotic metabolism in all species, and various papers are devoted to metabolism by man, nonhuman primates, birds, fish. invertebrates, plants and micro-organisms, In addition, aspects of species differences in both Phase I and Phase II reactions are considered in a number of the papers. Pharmacokinetics, pharmacogenetics and the use of cell suspensions and cultures for metabolic studies are also discussed. In general, the papers are essentially review articles II,174 I
Cosrnrr
Toxicol.
Vol. 17. No. 4
401
considering the basic principles of various aspects of the subject, rather than presentations of the authors’ latest research findings. In this respect this volume differs from the series entitled Microsomes and Drug Oxidations reviewed earlier (Cired in F.C.7: 1970, 8, 546; ibid 1975, 13, 270; ibid 1978, 16, 383). Furthermore, the extraction of information from the book under review is greatly assisted by the excellent author and subject indexes. A publication to be recommended. Pathology of Laboratory Animals. Vols I & II. Edited by K. Benirschke, F. M. Garner and T. C. Jones. Springer-Verlag. Berlin, 1978. pp. 2225. DM 565.30 (2 vols). The need for a good textbook on the pathology of laboratory animals was felt several decades ago when experimental pathology and biochemistry were in their infancy. R. Jaffe gallantly responded to this need and in 1931 gathered the information then available into the first textbook of laboratory animal pathology. This remained the only reference book on this topic until 1958 when, together with P. Cohrs and H. Meessen and helped by a large group of collaborators, he produced a much enlarged version of his earlier work. Both of these excellent texts were written in German. Since 1958. some major advances have taken place in pathology and, furthermore, an increasing burden has been imposed on the pathologist by demands from consumers, industry and government agencies for safety assurances. These developments have made the availability of an up-to-date text, preferably written in English, an urgent necessity. An attempt to tackle part of the problem was made some years ago by E. Cotchin and F. J. C. Roe, who, in collecting together a series of articles on rodent pathology, provided considerable help for the harassed pathologist. but they left some important gaps unfilled. The two volumes named above go a long way towards meeting this urgent need. The first, which may be identified as dealing with ‘systematic pathology’, considers the disease processes in the so-called systems common to all mammals (the cardiovascular. nervous and respiratory systems. for example). The material presented is concerned not only with commonly occurring pathological features but also with more esoteric pathology. The latter is particularly important in toxicology, since rare lesions are more likely to be attributed in error to a test chemical than are commonly occurring ones. The second volume of this pair is devoted to special topics. The infective diseases are the most importantamong these, and a succession of contributors deals succinctly with the various disease processes caused by lower organisms, from viruses to protozoa and helminths. Somewhat surprisingly. tumours are included in this volume. Neoplasia is a proliferative disorder, and one of the major problems in pathology is to distinguish it from non-neoplastic proliferative conditions. It would therefore be an advantage il in future editions, the chapter on tumours could be included with the systematic pathology where conditions associated with non-neoplastic proliferation are