Dna And Free Radicals

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 latest edition has been comprehensively rewritten and updated (over 80% of the text is new), whilst maintaining the clarity of its predecessor. There is expanded coverage of isoprostanes and related compounds, mechanisms of oxidative damage to DNA and proteins (and the repair of such damage), the free radical theory of ageing and the roles played by reactive species in signal transduction, cell death, human reproduction, and other important biological events. Greater emphasis has also been placed on the methods available to measure reactive species and oxidative damage (and their potential pitfalls), as well as the importance of antioxidants in the human diet." "This book is recommended as a comprehensive introduction to the field for students, clinicians and researchers, and an invaluable companion to all those interested in the role of free radicals in the life and medical sciences."--BOOK JACKET.

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.

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.

"Oxidative stress" is used as the generic term describing the involve ment of reactive oxygen species in various human diseases. The scope of such a topic is becoming increasingly wide. The recent interest in radicals such as nitric oxide and the discovery of new mechanisms such as the effect of free radicals on redox sensitive proteins and genes are enlarging our understanding of the physiological role of free radicals. Oxidative stress is involved in numerous pathological. processes such as ageing, respiratory or cardiovascular diseases, cancer, neurological pathologies such as dementia or Parkinson's disease. It still remains difficult, however, to demonstrate by chemical measurement the in vivo production of free radicals and even more to realise their speciation. Therefore, the development of new tools and indicators is engrossing many researchers working in this field. Reliable indicators are abso lutely necessary not only to monitor the evolution of oxidative stress in patients but also to evaluate the efficiency of new antioxidant treat ments. The French Free radical club of Grenoble, the CERLIB has been involved for many years in the organisation of international training programs on methodology, in order to provide both theoretical and practical help to researchers from various countries. Such training sessions have been highly successful and participants value the oppor tunity to learn reliable techniques. This positive echo explains why the researchers of CERLIB decided, with the help of Prof. Dr. B. Kalyanaraman, to publish selected techniques on free radical re search.

Although free radicals perform some useful immune functions, they can also damage healthy cells through a process called oxidation. Antioxidants reduce the effect of free radicals by binding together with these harmful molecules, decreasing their destructive power. This book highlights various issues of free radical biology from the perspective of antioxidant defense mechanisms. It also provides useful information on gene modulation, radiation-generated reactive oxygen species-induced apoptosis in cancer, and environmental aspects associated with free radicals’ exposure on living systems.

Free radical species are generally short-lived due to their high reactivity and thus direct measurement and identification are often impossible. ESR is the only technique which has the potential for direct detection of radicals but in biological systems even these must be trapped by a spin-trapping agent. Thus most investigations involve recognition of indicators of the presence of radicals in vivo or "FOOTPRINTS" of radical-mediated damage. Techniques in Free Radical Research assembles and critically assesses the most relevant and reliable experimental approaches used towards the measurement of radicals and radical-mediated damage in chemical systems, in cells and in tissues under the following six headings: a) Footprints of DNA damage, b) Footprints of protein damage, c) Footprints of lipid peroxidation, d) Footprints of antioxidant consumption, e) Footprints via indirect radical assays, and f) Footprints via the availability of transition metal complexes.