As modern day society takes an increasing interest in outdoor activities, its exposure to sunlight has never been greater. As a consequence, countries throughout the world are experiencing a dramatic increase in the incidences of skin carcinomas and melanomas. From DNA photolesions to mutations, skin cancer and cell death provides an authoritative source of information for photobiologists interested in the series of genetic events that occur in the skin, and eventually lead to cancer. With contributions from eminent scientists in the field, this book includes the latest information on DNA photolesions and repair, as well as the key mechanisms of solar UV in skin cancer initiation and development. Significant information relating to UV-induced photolesions and mechanisms of skin tumour occurrence is also included. By providing the basic phenomena underlying the science and an overview of the biological events that take place when cells are exposed to solar UV radiation, From DNA photolesions to mutations, skin cancer and cell death is suitable to all researchers interested in the process of photocarcinogenesis.
From DNA Photolesions to Mutations, Skin Cancer and Cell Death
By Évelyne Sage, Régen Drouin, Mahmoud RouabhiaThe Royal Society of Chemistry
Copyright © 2005 European Society for Photobiology
All rights reserved.
ISBN: 978-0-85404-326-2Contents
Chapter 1 UVB and UVA induced formation of photoproducts within cellular DNA Jean Cadet, Thierry Douki, Jean-Pierre Pouget and Jean-Luc Ravanat, 1,
Chapter 2 Chemical sequencing profiles of photosensitized DNA damage R. Jeremy H. Davies, Sharon M. Starrs and Clarke S. Stevenson, 15,
Chapter 3 DNA damage induced by UVA radiation: role in solar mutagenesis Evelyne Sage, Daniel Perdiz, Pál Gróf, Anne Reynaud-Angelin, Thierry Douki, Jean Cadet, Patrick J. Rochette, Nathalie Bastien and Régen Drouin, 33,
Chapter 4 Mutations induced by UV and sunlight Gerd P. Pfeifer, Dong-Hyun Lee, Jung-Hoon Yoon and Young-Hyun You, 49,
Chapter 5 Mechanisms and mutagenic consequences of photoproduct bypass by replicative and DNA damage bypass polymerases John-Stephen Taylor, 57,
Chapter 6 The Ogg1 protein of Saccharomyces cerevisiae: properties and biological functions Serge Boiteux, 93,
Chapter 7 The role of a yeast homologue of the human phosphatase activator hPTPA in the cellular response to oxidative DNA damage Dindial Ramotar, Jocelyn David and Elliot Drobetsky, 103,
Chapter 8 DNA repair in RNA polymerase I transcribed genes Antonio Conconi, Vyacheslav A. Bespalov, Deirdre Fahy and Michael J. Smerdon, 123,
Chapter 9 Global genome nucleotide excision repair: key players and their functions Marcel Volker and Leon H.F. Mullenders, 149,
Chapter 10 Efficient repair of UV-induced DNA damage in terminally differentiated human keratinocytes Dennis H. Oh and Kelvin Yeh, 167,
Chapter 11 Reactivation of UV-damaged viruses and reporter genes in mammalian cells Andrew J. Rainbow, Photini Pitsikas, Colleen Caney, Ihor P. Boszko, Bruce C. McKay and Murray A. Francis, 181,
Chapter 12 Transcription of p53-regulated genes under transcriptional stress: implications for nucleotide excision repair Bruce C. McKay, Cecilia Becerril and Jennifer C. Spronck, 205,
Chapter 13 What a difference a wavelength makes: The role of p53 in nucleotide excision repair of UV-induced DNA damage Julie Desnoyers, Dindial Ramotar, Géraldine Mathonnet, Caroline Léger and Elliot A. Drobetsky, 219,
Chapter 14 p53 and p33ING1: Role in nucleotide excision repair of UV-damaged DNA K-John Cheung Jr. and Gang Li, 233,
Chapter 15 Nuclear and Non-nuclear signals leading to UV-induced apoptosis Momchil D. Vodenicharov and Girish M. Shah, 247,
Chapter 16 Opposing roles of UV-induced apoptosis in early skin cancer Wengeng Zhang and Douglas E. Brash, 269,
Chapter 17 Acquired activation of signalling pathways in skin tumours from DNA repair-deficient xeroderma pigmentosum patients Jean-Claude Ehrhart, Fabien P. Gosselet, Raphaél M. Culerrier and Alain Sarasin, 281,
Chapter 18 Chaos theory and self-organized criticality describe the DNA damage signal transduction network Daniel B. Yarosh, 293,
Subject Index, 307,
CHAPTER 1
UVB and UVA induced formation of photoproducts within cellular DNA
Jean Cadet, Thierry Douki, Jean-Pierre Pouget and Jean-Luc Ravanat
Table of contents
Abstract
1.1 Introduction 3
1.2 Distribution of UVB radiation-induced dimeric
pyrimidime photoproducts within cellular DNA 5
1.3 UVC and UVB-induced formation of monomeric base photoproducts 7
1.4 Damage induced by UVA radiation to cellular DNA 8
1.5 Conclusions 10
References 10
Abstract
Emphasis is placed in this short survey on recent aspects of the photochemistry of cellular DNA that involve both the effects of UVB and UVA radiations. Direct excitation of the purine and pyrimidine bases of DNA is known to mostly generate dimeric pyrimidine photoproducts in oxygen independent photoreactions. Interestingly, the twelve possible dimeric photoproducts at the four main bipyrimidine sites can now be singled out as dinucleoside monophosphates. This is achieved using a specific and sensitive assay that associates high performance liquid chromatography to tandem mass spectrometry (HPLC-MS/MS) operating in the electrospray ionization (ESI) mode. Thus, it was found that UVB irradiation of human monocyte cells gives rise predominantly to cis-syn cyclobutadithymine, thymine-cytosine pyrimidine(6-4) pyrimidone adduct and related cyclobutyl dimer. In contrast the dimeric photoproducts at (di)cytosine sites are generated in very low yields although characteristic tandem mutations of UV-B irradiation are observed at the latter CC sequences. Further, cytosine photohydrate and Dewar valence isomers of the (6-4) photoproducts are at the best minor UV-B photoproducts. Relevant information on UVA-sensitized oxidative damage to cellular DNA was gained from measurements using chromatographic methods and the modified comet assay. Thus, it was shown that 8-oxo-7,8-dihydro-2'-deoxyguanosine is the predominant DNA oxidation product, as mostly, the result of singlet oxygen oxidation. In addition, oxidized pyrimidine bases and DNA strand breaks whose formation involves •OH radical, are produced in much lower yields. Work is in progress to assess the UVA-induced formation of other markers of oxidative stress. These include on the one hand DNA-protein crosslinks and on the other hand DNA adducts with reactive aldehydes that arise from the breakdown of initially generated lipid peroxides.
1.1 Introduction
Solar UV radiation appears to be the main etiological factor responsible for the induction of skin cancers in human population. It is well established that UVB and UVA radiations act mostly on cellular DNA via direct and photosensitized reactions respectively [for earlier reviews, see 1,2]. Precise assessment of the final products of these photoreactions has been hampered for years by the lack of accurate and quantitative methods of measurement. This particularly concerns the individual determination of dimeric pyrimidine photoproducts including cis-syn cyclobutadi-pyrimidines (CPDs), pyrimidine (6-4) pyrimidone photoadducts (6-4PPs) and related valence Dewar isomers (DewarPPs) for which only limited information was available until recently. However, relevant data on the distribution and repair of the three latter classes of photoproducts within the DNA of plasmids, isolated cells and tissues were gained mostly from serological approaches. These include ELISA, RIA and immuno-dot-blot measurements together with immunostaining detection through the availability of monoclonal and polyclonal antibodies. We may also mention the recent development of an immunological method aimed at measuring CPDs and 6-4PPs in the DNA of isolated cells in association with the comet assay. Another suitable method that is receiving major attention is the ligation-mediated polymerase chain reaction (LM-PCR). This allows the mapping within DNA at the nucleotide resolution of dimeric pyrimidine photoproducts and particularly of CPDs, the latter lesions being revealed through the nicking activity of T4 endonuclease V. Thus, it was found that methylation of cytosine residues in 5'-CCG and 5'-TCG sequences leads to a 10-fold increase in the UVB formation of CPDs. Interestingly the latter lesions were found to constitute major p53 mutation hot spots in mouse skin tumors. It was also shown that accumulation of dimeric DNA photoproducts takes place at the same locations of the p53 gene in...
