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DNA stores and passes the genetic information of almost all living organisms. Its molecular structure and their intramolecular interactions are particularly suitable to maximize stability against oxidative stress and UV-light absorption. Yet the protection and repair strategies are still error-prone: DNA lesions are produced, including the most complex and highly mutagenic ones. An important threat to DNA stability comes from photosensitization, i.e. from the dramatic multiplication of radiation-induced defects mediated by the presence of organic or organometallic dyes compared to the direct exposure to UVA radiation. Moreover, the photo-induced production of singlet oxygen generates an extremely high oxidative stress on DNA that, in vivo, normally results in extended cellular apoptosis. Elucidating the processes leading to DNA damages, from the production of a simple radical entity to deleterious lesions, as well as the opportunities of repair by devoted enzymes, is a cornerstone towards the development of more efficient protection strategies. Sensitization and selective production of DNA lesions can also be exploited to induce the selective apoptosis of cancer cells upon exposition to radiation or to oxidative stress, for instance in the field of photodynamic therapy. The importance and relevance of the field is witnessed by the impressive amount of high-level papers dealing with this complex subject, and notably tackling the structural elucidation of DNA and DNA-drug adducts, the mechanisms of formation of DNA lesions (including the precise detection of the final lesion products), as well as the influence of the lesions on the DNA stability and dynamics and the consequences on the ease of repair. Due to the complexity of the field lying at the frontiers between chemistry, physics and biology, multidisciplinary strategies allying modeling and experience are needed. This topic aims at giving an extended overview of the current research in the domain, with fundamental contribution from the leading groups in the field of DNA reactivity, structural characterization, photo-chemistry and photo-physics, as well as repair mechanism. It will therefore be a fundamental guide for scientists wanting to address the field of DNA lesion and repair, but also more generally for researchers working in rational drug design or in the development of biomarkers and medical imaging techniques
DNA stores and passes the genetic information of almost all living organisms. Its molecular structure and their intramolecular interactions are particularly suitable to maximize stability against oxidative stress and UV-light absorption. Yet the protection and repair strategies are still error-prone: DNA lesions are produced, including the most complex and highly mutagenic ones. An important threat to DNA stability comes from photosensitization, i.e. from the dramatic multiplication of radiation-induced defects mediated by the presence of organic or organometallic dyes compared to the direct exposure to UVA radiation. Moreover, the photo-induced production of singlet oxygen generates an extremely high oxidative stress on DNA that, in vivo, normally results in extended cellular apoptosis. Elucidating the processes leading to DNA damages, from the production of a simple radical entity to deleterious lesions, as well as the opportunities of repair by devoted enzymes, is a cornerstone towards the development of more efficient protection strategies. Sensitization and selective production of DNA lesions can also be exploited to induce the selective apoptosis of cancer cells upon exposition to radiation or to oxidative stress, for instance in the field of photodynamic therapy. The importance and relevance of the field is witnessed by the impressive amount of high-level papers dealing with this complex subject, and notably tackling the structural elucidation of DNA and DNA-drug adducts, the mechanisms of formation of DNA lesions (including the precise detection of the final lesion products), as well as the influence of the lesions on the DNA stability and dynamics and the consequences on the ease of repair. Due to the complexity of the field lying at the frontiers between chemistry, physics and biology, multidisciplinary strategies allying modeling and experience are needed. This topic aims at giving an extended overview of the current research in the domain, with fundamental contribution from the leading groups in the field of DNA reactivity, structural characterization, photo-chemistry and photo-physics, as well as repair mechanism. It will therefore be a fundamental guide for scientists wanting to address the field of DNA lesion and repair, but also more generally for researchers working in rational drug design or in the development of biomarkers and medical imaging techniques.
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
Advances in Radiation Biology, Volume 17: DNA and Chromatin Damage Caused by Radiation outlines the different biological reactions to radiation. This book discusses the linear energy transfer and energy loss; DNA breaks and track structure; DNA radicals from water radicals; and radiation-induced strand breaks in isolated DNA. The radiation damage to DNA and its nearby environment; thiol radioprotectors and mechanism of action; radiolysis of water and track reactions; and computer simulation of higher order structure of DNA are also elaborated. This publication likewise covers the concept of chromatin structure; DNA supercoiling studied by sedimentation; measurement of radiation-induced DNA breakage; and analysis of damage in interphase cells. This volume is a useful reference to biologists and students concerned with DNA and chromatin damage caused by radiation.
The free-radical chemistry of DNA had been discussed in some detail in 1987 in my book The Chemical Basis of Radiation Biology. Obviously, the more recent developments and the concomitant higher level of understanding of mechanistic details are missing. Moreover, in the living cell, free-radical DNA damage is not only induced by ionizing radiation, but free-radical-induced DNA damage is a much more general phenomenon. It was, therefore, felt that it is now timely to review our present knowledge of free-radical-induced DNA damage induced by all conceivable free-radical-generating sources. Originally, it had been thought to include also a very important aspect, the repair of DNA damage by the cell’s various repair enzymes. Kevin Prise (Cancer Campaign, Gray Laboratory, L- don) was so kind to agree to write this part. However, an adequate description of this strongly expanding area would have exceeded the allocated space by much, and this section had to be omitted. The directors of the Max-Planck-Institut für Strahlenchemie (now MPI für Bioanorganische Chemie), Karl Wieghardt and Wolfgang Lubitz, kindly allowed me to continue to use its facilities after my retirement in 2001. Notably, our - brarian, Mrs. Jutta Theurich, and her right-hand help, Mrs. Rosemarie Schr- er, were most helpful in getting hold of the literature. I thank them very much. Without their constant help, this would have been very difficult indeed.
The first edition of this book, published in 1999 and called DNA Repair Protocols: Eukaryotic Systems, brought together laboratory-based methods for studying DNA damage and repair in diverse eukaryotes: namely, two kinds of yeast, a nematode, a fruit fly, a toad, three different plants, and human and murine cells. This second edition of DNA Repair Protocols covers mammalian cells only and hence its new subtitle, Mammalian Systems. There are two reasons for this fresh emphasis, both of them pragmatic: to cater to the interests of what is now a largely mammalocentric DNA repair field, and to expedite editing and prod- tion of this volume. Although DNA Repair Protocols: Mammalian Systems is a smaller book than its predecessor, it actually contains a greater variety of methods. Fourteen of the book’s thirty-two chapters are entirely new and areas of redundancy present in the first edition have been eliminated here (for example, now just two chapters describe assays for nucleotide excision repair [NER], rather than seven). All eighteen returning chapters have been revised, many of them ext- sively. In order to maintain a coherent arrangement of topics, the four-part p- titioning seen in the first edition was dispensed with and chapters concerned with ionizing radiation damage and DNA strand breakage and repair were re- cated to near the front of the book. Finally, an abstract now heads each chapter.
Basic Clinical Radiobiology is a concise but comprehensive textbook setting out the essentials of the science and clinical application of radiobiology for those seeking accreditation in radiation oncology, clinical radiation physics, and radiation technology. Fully revised and updated to keep abreast of current developments in radiation biology and radiation oncology, this fifth edition continues to present in an interesting way the biological basis of radiation therapy, discussing the basic principles and significant developments that underlie the latest attempts to improve the radiotherapeutic management of cancer. This new edition is highly illustrated with attractive 2-colour presentation and now includes new chapters on stem cells, tissue response and the convergence of radiotherapy, radiobiology, and physics. It will be invaluable for FRCR (clinical oncology) and equivalent candidates, SpRs (and equivalent) in radiation oncology, practicing radiation oncologists and radiotherapists, as well as radiobiologists and radiotherapy physicists.
This book provides up-to-date coverage of selected topics in nucleic acid oxidation. The topics have been selected to cover everything from basic chemical mechanisms, repair of damage and the biological and pathological meaning of DNA oxidation. The chapters are authored by leading, research active, international experts in the respective topics.