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The chemistry and biology of benz [a]anthracenes
109 There are now several excellent and up-to-date British textbooks of chemical pathology from which to choose but I shall be surprised if this one does not achieve popularity and become a best seller. If certainly deserves to do so. F.V. Flynn Professor of Chemical Pathology, Universiry College Hospital, London, UK
* * * * *
The Chemistry and Biology of Benz[a]anthracenes M.S. Newman, B. Tiemey and S. Veeraraghavan Cambridge University Press, Cambridge and New York, 1988,228 pp., ISBN 0 521 305446, f35.00 Cancer epidemiology worldwide points to environmental and dietary factors being responsible for a proportion of all human cancer. Following the establishment of the structure of sterols in 1930, and the isolation of benzo[ alpyrene from coal tar in 1933, the subsequent fifty years has witnessed intense research into the carcinogenic activity of all polycyclic aromatic hydrocarbons. The corollary that breaking metabolic pathways by means of chemical intermediates might lead to tumour regression has been a second objective within the clinical medicine field. The Cambridge Monographs fulfil these aims by reviewing recent concepts and latest advances in the chemistry and biology of these carcinogens. The first volume published in 1987 covered the chemistry, biology, analyses and occurrence of benzo(a]pyrene. The second volume in the series also published in 1987 reviewed the occurrence, syntheses, physical and chemical properties and biological effect of the cyclo[ a]phenanthrenes - the polycyclic aromatic compound structurally related to the steroids. This third volume published in June, 1988 describes the chemistry and biological effects of the benz[ a]anthracenes and its derivatives. Volume 3 of the Monograph series is divided into two parts. Part 1 details the syntheses of the bei@a]anthracenes (BA). For readers working in this field there is a comprehensive survey of the synthetic routes to BA from benzenes, nephalens, anthracenes, phenanthrene (D ring) and the older routes (rings B and C). There are 22 Tables completing Part 1 with detailed References numbering 372 relating to the syntheses of BA and its methyl, alkyl, aryl, chloro, bromo, fluoro, methoxy, hydroxy, amino, cyan0 and lactone derivatives. This immense task has been condensed into 81 pages and will serve as an excellent introduction and Reference source for all University, Government and industrial laboratories concerned with BA and its compounds. In Part 2 the biological properties of BA and its substituted derivatives are discussed. Because these compounds occur in the environment derived from the combustion of organic matter (coal, tobacco, etc.), they have been the subject of intense research activity. The second part is divided into four sections metabolism, interaction with cellular macro-molecules, mutagenicity and carcinogenicity. The author emphasises the complexity of cancer induction and the number of variables involved such as the dose, species, age, sex, mode of administration, duration of exposure and adequate statistical analyses. There is an excellent summary of the highly carcinogenic methyl substituted BA’s (7-MBA and 7,12-DMBA) with published data up to the end of 1986. There is a fascinating section on mammary cancer rapidly induced by 7,12 dimethyl BA and dependent on hormonal status as well as age, strain, and pregnancy. This volume rightly emphasises the remarkable series of experiments continued throughout the 1980’s which demonstrated the role of the metabolite BA 3,4-dihydrodiol, precursor to the bay region diol epoxide, as the ultimate carcinogenic metabohte. The section on DNA, RNA and protein interaction focuses attention on the significance of these intermediate metabolites for example 3,4-diol 1, 2 epoxide with tumoutigenicity lo- to 40-fold more than the parent hydrocarbon. The author has succeeded in condensing salient features of this complex problem by means of a concise, coherent and systematic approach. His style, as one would expect in this monograph series, is clear and precise. My one serious reservation concerns the environment. The preface tell us that BA is present in air, water and soil, There
110
are no data given in this volume for the benefit of environmental hygienists in industry, in environmental regional laboratories or in the community. Frequently such data is required when opinions are expressed on environmental hazards due to the presence of carcinogenic agents, often raised by self-appointed pressure groups. In summary, these three volumes should be on the bookshelves of all laboratories. As teaching models for Universities and Colleges they are specialised text-books demonstrating the application of scientific methods by manipulation of radicals the position of which in the parent compound may radically alter the carcinogenicity. Furthermore, the principles involved, with the rapid progress achieved in the last fifty years, provide incentives for young scientists to solve the problem of human tumour growth. We are promised further monographs on more general subjects such as the use of short-term tests for carcinogenicity, the importance of pharmacodynamics, and the choice of animals in carcinogenic screening. These will be eagerly awaited by all workers in this field. William Taylor Emeritus Professor of Occupational Medicine, Wick, Caithness, Scotland
* * * * * The Alpha I Adrenergic Receptors
Edited by R.R. Ruffolo Humana Press (distributed by Wiley, Chichester, UK), 1988, 507
pp.,
S74.10
This is an excellent book for those who wish to delve into the animal pharmacology of alpha-l adrenergic receptors. The authors are a group of very distinguished American pharmacologists who each give a clear and concise account of their chosen area. The style is remarkably consistent in each chapter, beginning normally with what was the current thinking ten years ago followed by a comprehensive review of more recent data and culminating in an up-to-date summary of current knowledge. One feature which is particularly helpful in most chapters is the presence of a table in which all published work is listed so that it is easy to compare the results in one tissue with the results in a different tissue. There are however two limitations to the general use of this book. Firstly, the majority of the text concerns the vascular tree and the central nervous system. Admittedly this is where most of the work on (or receptors has taken place but any potential reader who wished to learn more about the or receptors in the kidney, liver or lung would find little to satisfy him in this text. Secondly, the vast majority of the text concerns animal pharmacology and little is said about the clinical pharmacology of these receptors in man except for a brief 16 pages (out of a total of 540 pages) at the back on therapeutic targets. The book starts with a historical perspective and then moves on to describe the basic pharmacology of the or receptor. Methods such as l&and binding studies and autoradiography are explained in such clear detail that any investigator who wished to try these techniques for the first time would be well advised to read this book. This includes an excellent guide to the potential pitfalls associated with each technique. Chapters 4 and 5 provide an excellent review of the role of Ca2+ mobilisation and, phosphatidylinositol turnover as they relate to the stimulation of a, receptors. Further chapters then deal in turn with at receptors in the vascular tree and in the central nervous system. As mentioned above, this is an excellent text for biochemists and pharmacologists interested in an up-to-date and very readable text on Q, receptors but it does not concern itself much with the clinical aspects of these receptors. Allan D. Struthers Consultant Physician, Ninewells Hospital and Medical School, Dundee, UK
* * * * *
The Chemistry and Biology of Benz[a]anthracenes M.S. Newman, B. Tiemey and S. Veeraraghavan Cambridge University Press, Cambridge and New York, 1988,228 pp., ISBN 0 521 305446, f35.00 Cancer epidemiology worldwide points to environmental and dietary factors being responsible for a proportion of all human cancer. Following the establishment of the structure of sterols in 1930, and the isolation of benzo[ alpyrene from coal tar in 1933, the subsequent fifty years has witnessed intense research into the carcinogenic activity of all polycyclic aromatic hydrocarbons. The corollary that breaking metabolic pathways by means of chemical intermediates might lead to tumour regression has been a second objective within the clinical medicine field. The Cambridge Monographs fulfil these aims by reviewing recent concepts and latest advances in the chemistry and biology of these carcinogens. The first volume published in 1987 covered the chemistry, biology, analyses and occurrence of benzo(a]pyrene. The second volume in the series also published in 1987 reviewed the occurrence, syntheses, physical and chemical properties and biological effect of the cyclo[ a]phenanthrenes - the polycyclic aromatic compound structurally related to the steroids. This third volume published in June, 1988 describes the chemistry and biological effects of the benz[ a]anthracenes and its derivatives. Volume 3 of the Monograph series is divided into two parts. Part 1 details the syntheses of the bei@a]anthracenes (BA). For readers working in this field there is a comprehensive survey of the synthetic routes to BA from benzenes, nephalens, anthracenes, phenanthrene (D ring) and the older routes (rings B and C). There are 22 Tables completing Part 1 with detailed References numbering 372 relating to the syntheses of BA and its methyl, alkyl, aryl, chloro, bromo, fluoro, methoxy, hydroxy, amino, cyan0 and lactone derivatives. This immense task has been condensed into 81 pages and will serve as an excellent introduction and Reference source for all University, Government and industrial laboratories concerned with BA and its compounds. In Part 2 the biological properties of BA and its substituted derivatives are discussed. Because these compounds occur in the environment derived from the combustion of organic matter (coal, tobacco, etc.), they have been the subject of intense research activity. The second part is divided into four sections metabolism, interaction with cellular macro-molecules, mutagenicity and carcinogenicity. The author emphasises the complexity of cancer induction and the number of variables involved such as the dose, species, age, sex, mode of administration, duration of exposure and adequate statistical analyses. There is an excellent summary of the highly carcinogenic methyl substituted BA’s (7-MBA and 7,12-DMBA) with published data up to the end of 1986. There is a fascinating section on mammary cancer rapidly induced by 7,12 dimethyl BA and dependent on hormonal status as well as age, strain, and pregnancy. This volume rightly emphasises the remarkable series of experiments continued throughout the 1980’s which demonstrated the role of the metabolite BA 3,4-dihydrodiol, precursor to the bay region diol epoxide, as the ultimate carcinogenic metabohte. The section on DNA, RNA and protein interaction focuses attention on the significance of these intermediate metabolites for example 3,4-diol 1, 2 epoxide with tumoutigenicity lo- to 40-fold more than the parent hydrocarbon. The author has succeeded in condensing salient features of this complex problem by means of a concise, coherent and systematic approach. His style, as one would expect in this monograph series, is clear and precise. My one serious reservation concerns the environment. The preface tell us that BA is present in air, water and soil, There
110
are no data given in this volume for the benefit of environmental hygienists in industry, in environmental regional laboratories or in the community. Frequently such data is required when opinions are expressed on environmental hazards due to the presence of carcinogenic agents, often raised by self-appointed pressure groups. In summary, these three volumes should be on the bookshelves of all laboratories. As teaching models for Universities and Colleges they are specialised text-books demonstrating the application of scientific methods by manipulation of radicals the position of which in the parent compound may radically alter the carcinogenicity. Furthermore, the principles involved, with the rapid progress achieved in the last fifty years, provide incentives for young scientists to solve the problem of human tumour growth. We are promised further monographs on more general subjects such as the use of short-term tests for carcinogenicity, the importance of pharmacodynamics, and the choice of animals in carcinogenic screening. These will be eagerly awaited by all workers in this field. William Taylor Emeritus Professor of Occupational Medicine, Wick, Caithness, Scotland
* * * * * The Alpha I Adrenergic Receptors
Edited by R.R. Ruffolo Humana Press (distributed by Wiley, Chichester, UK), 1988, 507
pp.,
S74.10
This is an excellent book for those who wish to delve into the animal pharmacology of alpha-l adrenergic receptors. The authors are a group of very distinguished American pharmacologists who each give a clear and concise account of their chosen area. The style is remarkably consistent in each chapter, beginning normally with what was the current thinking ten years ago followed by a comprehensive review of more recent data and culminating in an up-to-date summary of current knowledge. One feature which is particularly helpful in most chapters is the presence of a table in which all published work is listed so that it is easy to compare the results in one tissue with the results in a different tissue. There are however two limitations to the general use of this book. Firstly, the majority of the text concerns the vascular tree and the central nervous system. Admittedly this is where most of the work on (or receptors has taken place but any potential reader who wished to learn more about the or receptors in the kidney, liver or lung would find little to satisfy him in this text. Secondly, the vast majority of the text concerns animal pharmacology and little is said about the clinical pharmacology of these receptors in man except for a brief 16 pages (out of a total of 540 pages) at the back on therapeutic targets. The book starts with a historical perspective and then moves on to describe the basic pharmacology of the or receptor. Methods such as l&and binding studies and autoradiography are explained in such clear detail that any investigator who wished to try these techniques for the first time would be well advised to read this book. This includes an excellent guide to the potential pitfalls associated with each technique. Chapters 4 and 5 provide an excellent review of the role of Ca2+ mobilisation and, phosphatidylinositol turnover as they relate to the stimulation of a, receptors. Further chapters then deal in turn with at receptors in the vascular tree and in the central nervous system. As mentioned above, this is an excellent text for biochemists and pharmacologists interested in an up-to-date and very readable text on Q, receptors but it does not concern itself much with the clinical aspects of these receptors. Allan D. Struthers Consultant Physician, Ninewells Hospital and Medical School, Dundee, UK