UKEMS/Dutch EMS-sponsored workshop on biomarkers of exposure and oxidative DNA damage & 7th GUM-32P-postlabelling workshop, University of Münster, Münster, Germany, 28–29 March 2011†

Volker M. Arlt 0 2 4 Tanja Schwerdtle 0 1 2 4 0 The United Kingdom Environmental Mutagen Society (UKEMS), the Dutch Environmental Mutagen Society (Dutch EMS) and the German Environmental Mutagen Society (GUM) sponsored a 2-day workshop (28-29 March 2011) at the University of Mu nster in Mu nster, Germany, on biomarkers of exposure and oxidative damage to DNA to gain a greater understanding of environmental cancer risks and their mod- ulation (1,2). After nearly 5 years, this is the second in- ternational workshop on this topic after the first one was held in September 2006 in Heidelberg, Germany, jointly sponsored by the Environmental Cancer Risk , Nutrition and Individual 1 Institute of Food Chemistry, University of Mu nster , Corrensstrasse 45, 48149 Mu nster , Germany 2 Section of Molecular Carcinogenesis, Institute of Cancer Research , Brookes Lawley Building, Sutton, Surrey SM2 5NG , UK 3 P-Postlabelling workshop in Munich 4 Speakers: Volker M.Arlt (Institute of Cancer Research, UK), Frederick A.Beland (National Center for Toxicological Research; USA), Karen Brown (University of Leicester, UK), Marcus Cooke (University of Leicester, UK), Andrew Collins (University of Oslo, Norway), Silvio De Flora (University of Genoa, Italy), Eugenia Dogliotti (Istituto Superiore di Sanita`, Italy), Bernd Epe (University of Mainz, Germany), Peter B. Farmer (University of Leicester, UK), Hansruedi Glatt (German Institute of Human Nutrition, Germany), Roger W. Godschalk (University of Maastricht, The Netherlands), Stephen S. Hecht (University of Minnesota, USA), Hanna L. Karlsson (Karolinska Institute, Sweden), Micheline Kirsch-Volders (Vrije Universiteit Brussels, Belgium), Soterios Kyrtopoulos (National Hellenic research Foundation, Greece), Steffen Loft (University of Copenhagen , Denmark) , Ryszard Olinski (Nicolaus Copernicus University , Poland) , David H.Phillips (Institute of Cancer Re- search, UK), Miriam C. Poirier (National Cancer Institute, USA), Roel Schins (University of Du sseldorf, Germany), Heinz H. Schmeiser (German Cancer Research Center, Germany), Tanja Schwerdtle (University of Mu nster, Germany), Albrecht Seidel (Biochemical Institute for Environmental Carci- nogens, Germany), Gu nter Speit (University of Ulm, Germany), Marie Stiborova (Charles University Prague, Czech Republic), Helga Stopper (University of Wu rzburg, Germany), Jan Topinka (Institute of Experimental Medicine AS, Czech Republic), frederik-Jan van Schooten (University of Maastricht, The Netherlands) and Roel Vermeulen (Utrecht University , The Netherlands) *To whom correspondence should be addressed. Tel: 44 20 8722 4405; Fax: 44 20 8722 4052; Email: Environmental exposures are a major concern for human cancer. However, the precise contribution of specific risk factors and their interactions, both with each other and with genotype, continue to be difficult to elucidate. The exposome is the comprehensive characterisation of an individual's lifetime exposure history (Wild, C. P. (2009) Environmental exposure measurement in cancer epidemiology. Mutagenesis, 24, 117-125). Unravelling complex environmental and genetic aetiologies in order to plan effective public health interventions demands that both environmental exposures and genetic variations are reliably measured. The development, validation and application of biomarkers of exposure are manifestly critical to the future of cancer epidemiology. The aim of this workshop at the University of Mu nster was to discuss the current status of exposure biomarkers in cancer molecular epidemiology as well as new findings achieved by applying the methods to studies of mechanisms of human cancer. Day 1 focused on biomarkers of exposure (i.e. carcinogen DNA adducts), effect and susceptibility to gain greater understanding of environmental cancer risks and their modulation. Day 2 focused on the role of oxidative stress and DNA damage in human carcinogenesis including methodologies used for the measurement of oxidatively induced DNA lesions in human cells or tissues and the possible use of these lesions as cancer biomarkers. - Susceptibility (ECNIS) EU Network of Excellence and the GUM (3). The workshop in Munster provided a unique forum bringing together scientists working in this research area from Europe, USA, South America and Asia. More than 180 researchers from 20 countries took part. Within the workshop, 29 lectures were given and nearly 80 posters presented. The opening keynote lecture entitled Carcinogen biomarkers for investigating tobacco and cancer was given by Stephen Hecht (University of Minnesota, USA). Among lifestyle factors definitely related to cancer, tobacco use arguably entails the largest human exposure to diverse chemical carcinogens including tobacco-specific nitrosamines [e.g. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)], aldehydes and polycyclic aromatic hydrocarbons (PAHs) (4). People exposed to secondhand tobacco smoke (SHS) inhale the lung carcinogen NNK, which is metabolised to NNAL which can be measured in urine and has emerged as an excellent biomarker of NNK uptake. Urine samples from 79 children exposed to SHS were analysed for total NNAL (5). The study showed that children were nearly all exposed to NNK due mainly to exposure to SHS from adult smokers in their homes implicating that adult smokers should adopt restrictions to protect their children from SHS. Another validated biomarker of PAH exposure is r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and urinary levels of PheT and NNAL in relation to lung cancer development in cigarette smokers were examined in the Shanghai Cohort Study (6). This casecontrol study nested within the cohort included 475 lung cancer patients (cases) who smoked cigarettes at recruitment and 475 current smokers (controls). Urinary levels of PheT and NNAL were significantly higher for cases than controls after adjustment for smoking intensity and duration confirming them as risk biomarkers for lung cancer in smokers. Albrecht Seidel (Biochemical Institute for Environmental Carcinogens, Germany) reported that the determination of urinary-excreted PAH metabolites (e.g. of pyrene and phenanthrene) can be used in human biomonitoring at the workplace (7,8). The occupational settings included employees of a manufacturer of graphite electrodes, employees of a coking plant and employees feeding converters during steel production. Overall, phenanthrene diols appeared to be sensitive biomarkers of PAH exposure. The various types of phenanthrene metabolites (phenols, diols and phenanthrene tetrol) could probably be used in future studies for phenotyping of individuals to determine their possible susceptibility to develop cancer upon exposure to PAH mixtures. Silvio De Flora (University of Genoa, Italy) delivered a talk on Induction of biomarker and tumours by cigarette smoke (CS) and their chemoprevention. Chemopreventi (...truncated)