An encyclopedia of polyamines

Most textbooks that deal with biochemistry, molecular biology or cell biology either ignore polyamines completely or provide a highly abbreviated and frequently incorrect mention. This is a most-unfortunate lapse because polyamines are ubiquitous cellular components that play critical roles in many aspects of cellular physiology, including cell growth, differentiation and neoplastic transformation. In his monumental treatise A Guide to the Polyamines, Seymour Cohen attempts single handedly to redress the balance. This book, which is almost 600 pages long, could be subtitled `Everything you always wanted to know about polyamines but were afraid to ask'.Cohen has been a leading and revered figure in polyamine research for many years while also achieving international recognition in several other fields, including virology, anti-cancer drug development and studies of the history of science. These other interests, particularly the latter, come through in this book—which, for example, contains a seven-page time line (that starts in the 8th century) of important events in the field.The book provides very detailed coverage of microbial and mammalian polyamine metabolism, the role of polyamines in neoplastic growth and the possible use of inhibitors and antagonists of polyamines as anti-cancer agents. These topics have been the subject of a number of detailed review articles, but Cohen's book provides another and even-more-detailed source for the reader who is interested in these concepts. Perhaps even more valuable are the chapters on viral and plant polyamines. There is a wealth of fascinating and instructive work on these systems, which is frequently but mistakenly ignored by scientists who are interested in mammals. Cohen, who has contributed significantly to studies of both viral and plant polyamines, provides an erudite and readable account of this work.There is also an excellent chapter on polyamines in protozoal parasites. The ability to cure African sleeping sickness caused by Trypanasoma brucei gambiense by using the ornithine decarboxylase (ODC) inhibitor α-difluoromethylornithine (DFMO) is a major achievement in the polyamine field. DFMO was designed and synthesized as a highly specific enzyme-activated inhibitor of ODC. Cohen provides a comprehensive review of this work and of the possible reasons for the effectiveness of this drug. He also correctly points out the problems of affordability in using DFMO in countries in which African sleeping sickness is endemic. This is a critical issue that needs to be considered in detail by grant-giving agencies. The use of modern molecular biological and mechanism-based drug design to develop agents that are capable of treating diseases that affect millions of people in the third world is supported strongly by such agencies, particularly because novel biochemical pathways provide fascinating potential targets. However, it is unlikely that such compounds will ever be available at costs that can be met locally. DFMO, which by comparison with many modern drugs is not particularly costly, provides an excellent example of this paradox. The lack of support for studies that aim to build on the success of DFMO (by synthesizing derivatives that have better bioavailability/ pharmacokinetic properties, or by developing inexpensive agents that synergize with DFMO in order to reduce the costs of treatment) highlights this problem.The only serious problem with this book is that its length may prove daunting to potential readers. Some chapters appear to be unnecessarily detailed; for example, the chapter on analysis of polyamines contains detailed coverage of many outdated and impractical methods, and several illustrations in which the peaks in amine separations are not identified. Also, it is doubtful whether readers of this book need figures that show the mass spectra of trifluoroacetylated polyamines.The book is so comprehensive and scholarly that it is an amusing exercise for persons who have also been in the polyamine field for a long time to attempt to find something that has been left out. There is excellent coverage of the salvage reactions by which 5′-methylthioadenosine (MTA), the side product in the aminopropyltransferase reactions that lead to the generation of polyamines, is recycled into the methionine and adenine nucleotide pools. The absence of the key enzyme in this recycling, MTA phosphorylase, in many tumor cells and the possible use of this deficiency for chemotherapy are described. However, the reader is not provided with the molecular basis for this deficiency, which occurs because of the proximity of the MTA phosphorylase gene to the p16INK4 tumor-suppressor gene.The coverage of the use of transgenic mice to investigate the role of ODC in tumor promotion seems somewhat unbalanced and out of date. The book describes in some detail the rather modest increase in frequency of skin carcinogenesis that was observed in transgenic mice that express the human ODC gene (in addition to the endogenous copy) and have an increased synthesis of putrescine (presumably because of the increased ODC-gene copy number). However, it provides only the briefest mention of the more-easily interpreted studies, performed by O'Brien and colleagues, in which a truncated and stable ODC was expressed at high levels in murine skin by using the keratin-6 promoter.These are extremely minor quibbles, however. This book will point the interested reader in any direction concerning polyamines that he or she wishes to go. It is the type of detailed review of a field that sadly appears only rarely in print and even more rarely on the shelves of libraries that have limited budgets. I will certainly urge my graduate students to read it in detail, although its length and breadth might prevent them from doing so.