Free Radical Induced Dna Damage And Its Repair

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 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.

Written by renowned biologists and medical scientists specializing in the field, this volume offers a comprehensive account of the role of oxidative stress and DNA damage in human disease. Emphasizes the role played by free radicals; examines the fundamental mechanisms underlying the pathology of human diseases; shows how DNA is an important target in cellular damage; and outlines the pioneering studies relating to the chemistry of DNA damage. MARKETS: " For research and development personnel in academia and industry involved in investigating drugs and toxic compounds; and for pharmacologists, pathologists, oncologists, chemotherapists, biochemists, chemists, physiologists, biologists, and all those interested in DNA or free radical research.

This book is based on the papers presented at the conference on "Mecha nisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment," held at the National Bureau of Standards on June 2-7, 1985, This volume deals with mechanisms of DNA damage and repair at the molecular level; consequences of unrepaired or misrepaired damage, with major emphasis on carcinogenesis; drugs which bind selectively to altered and potentially damaging DNA sequences; and potential utilization of DNA damage as an endpoint for assessing risks of UV light, ionizing radiations, chemicals, drugs, and hazardous agents in foods. Because the induction of mutations by radiation and genotoxic chemicals has been observed to follow one-hit kinetics in some instances, it is generally assumed that any level of exposure to a DNA-damaging agent may increase the risk of genetic disease or cancer in an exposed population. At the same time, however, there is evidence that although the DNA of living cells is continually damaged by natural background radiation, free radicals, and other naturally occurring processes, most of the damage is normally repaired.

In recent years the field of DNA repair has flourished due to new findings on DNA repair mechanisms and the molecular basis of cancer. This volume covers the most recent developments in this research field and contains contributions from scientists working in various fields.

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

Cutting edge reviews by leading researchers illuminate key aspects of DNA repair in mammalian systems and its relationship to human genetic disease and cancer. Major topics include UV and X-Ray repair, repair of chemical damage, recombinational repair, mismatch repair, transcription-repair coupling, and the role of DNA repair in disease prevention. Extensive up-to-date references and rigorous peer-review of each chapter make this volume definitive and bring it to the active frontiers of research.

This book is intended for students and scientists working in the field of DNA repair, focusing on a number of topics ranging from DNA damaging agents and mechanistic insights to methods in DNA repair and insights into therapeutic strategies. These topics demonstrate how scientific ideas are developed, tested, dialogued, and matured as it is meant to discuss key concepts in DNA repair. The book should serve as a supplementary text in courses and seminars as well as a general reference for biologists with an interest in DNA repair.