E-Book Overview
Understanding of the molecular basis of DNA damage and its repair has increased dramatically in recent years, and substantial knowledge now exists concerning the products arising from free-radical attack on DNA. Free-radical DNA damage may lead to mutations, cancer, and cell death. Free radicals have various sources, notably ionizing radiation and oxidative stress. In radiotherapy for cancer and with some anticancer drugs, use is made of cell death by excessive DNA damage. The mechanisms leading to products of free-radical attack which have been studied in models and with small double-stranded DNA fragments are discussed in detail, and the basics of the underlying free-radical chemistry are dealt with in separate chapters.
E-Book Content
Clemens von Sonntag
Free-Radical-Induced DNA Damage and Its Repair A Chemical Perspective
Clemens von Sonntag
Free-Radical-Induced DNA Damage and Its Repair A Chemical Perspective
With 13 Figures and 100 Tables
123
Professor Dr. Clemens von Sonntag Bleichstr. 16 D-45468 Mühlheim Germany
ISBN-10 3-540-26120-6 Springer-Verlag Berlin Heidelberg New York ISBN-13 978-3-540-26120-9 Springer-Verlag Berlin Heidelberg New York Libary of Congress Control Number: 2005926889 This work is subjekt to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must be obtained from Springer-Verlag. Violations are liable to prosecution under the German Copyright Law. Springer is a part of Springer Science+Business Media springeronline.com © Springer-Verlag Berlin Heidelberg 2006 Printed in Germany The use of general descriptive names, registered names, trademarks, etc. in this publications does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Editor: Dr. Sabine Schreck, Heidelberg Desk Editor: Anette Lindqvist, Heidelberg Typesetting: Satz-Druck-Service, Leimen Cover-Design: design & production, Heidelberg Printed on acid-free paper 31/3151Re
5 4 3 2 1 0
Preface
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, London) 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