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Comprehensive theoretical and experimental analysis of UV-radiation and low energy electron induced phenomena in nucleic acid bases (NABs) and base assemblies are presented in this book. NABs are highly photostable; the absorbed energy is dissipated in the form of ultrafast nonradiative decay. This book highlights the possible mechanisms of these phenomena which is important for all living species and discusses technical challenges in exploration of these processes.
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
Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada, the USA and Australia. This book summarizes the advances achieved by these research groups after more than ten years of studies on radiation damage in biomolecular systems. An extensive Part I deals with recent experimental and theoretical findings on radiation induced damage at the molecular level. It includes many contributions on electron and positron collisions with biologically relevant molecules. X-ray and ion interactions are also covered. Part II addresses different approaches to radiation damage modelling. In Part III biomedical aspects of radiation effects are treated on different scales. After the physics-oriented focus of the previous parts, there is a gradual transition to biology and medicine with the increasing size of the object studied. Finally, Part IV is dedicated to current trends and novel techniques in radiation reserach and the applications hence arising. It includes new developments in radiotherapy and related cancer therapies, as well as technical optimizations of accelerators and totally new equipment designs, giving a glimpse of the near future of radiation-based medical treatments.
The covalent attachment to deoxyribonucleic acid in vivo of a large number of different types of chemical compounds (both normal cellular constituents such as proteins and amino acids, and also exogenous compounds such as drugs, carcinogens, etc. ) have been shown to exert profound effects upon cells. Four research activi ties, formerly considered to be totally independent, relate to this problem of nucleic acid adducts--(1) normal covalent attachment of DNA to membranes, protein linkers in chromosomes, etc. ; (2) the roles of radiation and chemical enhancement of DNA adduct formation in cell killing and mutagenesis. (A related field is the use of known cross-linking reactions to gain information on structural associations in macromolecular complexes. ); (3) the relevance of DNA adducts to chemical and radiation carcinogenesis; (4) the rele vance of DNA adducts to the cross-linking theory of cellular aging. (1) There are numerous examples of normal linkages between DNA and protein, e. g. , DNA-membrane attachment sites, protein linkers in chromosomes, amino acids covalently linked to DNA as a function of growth conditions, and gene regulation by non-covalently bound proteins. A summary of data on natural adducts to DNA thus serves to introduce the subject of the radiation and chemical enhancement of DNA adduct formation. (2) In the past, radiation biology has been concerned mainly with trying to understand the radiation chemistry of purified DNA, and the biological effects and repair of these radiation-induced alterations when produced in cellular DNA.
Photochemistry and Photobiology of Nucleic Acids: Volume II, Biology is a collection of papers that deals with the biological effects due to stable UV induced alterations in critical cellular macromolecules, including cell death, growth delay, mutagenesis, and carcinogenesis. The papers assume that DNA is the macromolecule most relevant to cell pathology, as well as to the photochemical and photobiological properties of RNA which are essential in cellular functions. One paper investigates the UV-induced cross-linkings of proteins with nucleic acids as a possible cause of biological effects other than just in terms of the damage done to nucleic acids. Other papers discuss the mechanisms of protection against, and in the repair of damage caused by UV photons and by ionizing radiation (also chemical mutagens) in many organisms from viruses to mammalian cells. The repair processes appear to play a role in monitoring and preserving the structural integrity of DNA during physiological processes such as replication and transcription. One paper notes that in experiments on human embryonic lung fibroblasts WI-38 at very high radiation doses, radiation products of Thy in acid-soluble form appear while products from the DNA (acid-precipitable fraction) disappear. The paper suggests that the excision process is therefore selective. The collection is suitable for biochemists, microbiologists, or academicians whose works involve genetics, cancer, and cellular research.
Concepts in Radiation Cell Biology summarizes current concepts related to the effects of radiation on cell biology, with emphasis on the underlying macromolecular basis for cellular changes in irradiated cells. It explores the effects of non-ionizing radiation, such as ultraviolet and visible light; the use of laser light in cellular studies; and the biological effects of ionizing radiation on cells. Results of ultraviolet studies implicating DNA as the main target macromolecule responsible for radiation injury, such as division delays, lethality, and delayed DNA replication, are presented. Divided into eight chapters, this volume begins with an overview of ultraviolet irradiation of DNA as well as the physical and biological properties of irradiated DNA. It then discusses methods used in the photoinactivation of viruses; the effects of ultraviolet radiation on bacteria; radiation-induced biochemical changes in protozoa; and techniques for the analysis of radiation-induced mitotic delay in synchronously dividing sea urchin eggs. The book also covers the effects of radiation on mammalian cells; the effects of ionizing radiation on higher plants; and the photodynamic effects of laser light on cells. This book is a valuable resource for cell biologists, as well as students and investigators who are seeking the necessary information for further experimentation in radiation cell biology.