TY - JOUR
AU - Schmeiser, Heinz H.
AB - Abstract Speakers: Volker M.Arlt (Institute of Cancer Research, UK), Frederick A.Beland (National Center for Toxicological Research; USA), Karen Brown (University of Leicester, UK), Erwin Eder (University of Würzburg, Germany), Gerhard Eisenbrand (University of Kaiserslautern, Germany), Peter B.Farmer (Biocentre Leicester, UK), Panagiotis Georgiadis (National Hellenic Research Foundation, Greece), Hansruedi Glatt (German Institute of Human Nutrition, Germany), Roger W.Godschalk (University of Maastricht, The Netherlands), Arthur P.Grollman (State University of New York at Stony Brook, USA), Monica Hollstein (German Cancer Research Center, Germany), Werner Lutz (University of Würzburg, Germany), Matilde M.Marques (Technical University of Lisbon, Portugal), Lennart Möller (Karolinska Institute, Sweden), Christopher J.Michejda (National Cancer Institute Frederick, USA), Jagadeesan Nair (German Cancer Research Center, Germany), Marco Peluso (Tuscany Cancer Institute, Italy), Wolfgang Pfau (GAB-Consulting; Germany), David H.Phillips (Institute of Cancer Research, UK), Elmar Richter (University of Munich, Germany), Heinz H.Schmeiser (German Cancer Research Center, Germany), Oliver J.Schmitz (University of Wuppertal, Germany), Bernadette Schoket (National Institute of Environmental Health, Hungary), Dan Segerbäck (Karolinska Institute, Sweden), Albrecht Seidel (Biochemical Institute for Environmental Carcinogens, Germany), Marie Stiborova (Charles University Prague, Czech Republic), Jan Topinka (Institute of Experimental Medicine AS, Czech Republic). Of all the chemicals classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), 90% exert their biological effects through binding of their metabolically activated intermediates to DNA forming covalent DNA adducts. As a consequence DNA adducts are generally considered to be causative and directly related to tumour formation. DNA adduct analyses reflect tissue-specific rates of adduct formation and removal, which depend on carcinogen uptake, metabolic activation, DNA repair, adduct instability and tissue turnover and are thus useful markers of carcinogen exposure. The measurement of carcinogen–DNA adduct levels is central to the understanding of chemical carcinogenesis both in animals and humans to determine molecular mechanisms and exposure. Sensitive methods for DNA adduct analysis used to date are based on 32P-postlabelling, immunoassay, mass spectrometry and laser-induced fluorescence. The aim of this workshop held over 2 days (29–30 September 2006) at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, was to discuss methodological improvements of DNA adduct detection with emphasis on the 32P-postlabelling procedure as well as new findings achieved by applying the methods to studies on understanding human cancer mechanisms and to elucidate the relationship between adduct formation and human cancer risk. The Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) EU Network of Excellence and the German Environmental Mutagen Society (GUM) sponsored a 2 day workshop (29–30 September 2006) at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, on biomarkers of exposure, effect and susceptibility to gain a greater understanding of environmental cancer risks and their modulation. A major focus of the workshop was on DNA damage and DNA adduct detection and provided a unique forum bringing together scientists working in this field from Europe and the United States. More than 130 researchers from 15 countries took part. Within the workshop 28 lectures were given and 40 posters presented. A special symposium was dedicated to Prof. Manfred Wiessler, head of the Division of Molecular Toxicology, on the occasion of his 65th birthday, who will retire after 37 years service to the DKFZ. The workshop was organised to honour Prof. Wiessler's contributions to the field of environmental and molecular toxicology. The keynote lecture entitled ‘Acrylamide: adducts, mutations and cancer’ was given by Frederick A.Beland (National Center for Toxicological Research, USA). Acrylamide, a contaminant of baked and fried starchy foods is carcinogenic to animals. However, the mechanism of tumour formation is controversial, with both genotoxic and non-genotoxic pathways being proposed (1,2). Using high performance liquid chromatography (HPLC) coupled with electrospray ionization tandem mass spectrometry (MS) DNA adduct formation by acrylamide and its reactive metabolite glycidamide was investigated in rodents. Several major depurinating DNA adducts have been identified after in vitro reaction of glycidamide with DNA, including N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (N3-GA-Ade). In rodents, the extent of DNA binding by glycidamide was much higher than with acrylamide, whereby, the conversion of acrylamide to glycidamide was much more efficient in adult mice compared with adult rats. The formation of these DNA adducts is consistent with the previously reported mutagenicity of acrylamide and glycidamide in vitro. These data suggest that the carcinogenicity of acrylamide is mediated through its metabolism to glycidamide pointing to a genotoxic mechanism. David H.Phillips (Institute of Cancer Research, UK) delivered a talk on ‘Elucidating pathways of metabolic activation of carcinogens by quantifying and characterising their DNA adducts’. Using thin-layer chromatography (TLC) and HPLC to analyse the pattern and extend of DNA binding of metabolites and reactive derivatives of environmental carcinogens like polycyclic aromatic hydrocarbons (PAHs) (3) or drugs such as tamoxifen the 32P-postlabelling method can be a sensitive tool to elucidate their metabolic pathways. Thus, activation of tamoxifen has been shown to be mediated by α-hydroxylation and by sulfotransferases (4). In order to investigate the role of cytochrome P450 (CYP) enzymes in xenobiotic metabolism a transgenic mouse model (HRN™ mice) was presented (5,6). In HRN™ mice CYP oxidoreductase (POR), the unique electron donor to CYPs, is deleted specifically in the liver, resulting in the loss of essentially all hepatic CYP function (7). However, studies on benzo[a]pyrene-DNA adduct formation in HRN™ mice revealed an apparent paradox, whereby CYP1A1 seems to be more important for detoxification of benzo[a]pyrene in vivo despite being important for its metabolic activation in vitro. Lennart Möller (Karolinska Institute, Sweden) reported on ‘DNA adduct analyses of human tissues by the 32P-HPLC method’. Combining the 32P-postlabelling method with direct injection into a HPLC system with on-line detection of 32P couples the high sensitivity with a high resolution (8). Using this analytical system, DNA adduct measurements were reported from human white blood cells, biopsies of solid tumours, human placenta and autopsy liver samples. Such analyses reflected seasonal air pollution, could discriminate between polluted and control areas and detected a DNA adduct associated with colon cancer, although adduct patterns and levels showed great inter-individual variability. Several presentations focused on alternative methods to 32P-postlabelling for the detection of DNA adducts. Bernadette Schoket (National Institute of Environmental Health, Hungary) discussed ‘Immunoassays for the determination of PAH–DNA adducts’. After 32P-postlabelling, immunoassay is the second most sensitive method for the detection of PAH–DNA adducts in experimental samples and human tissues (9), of which the chemiluminescence immunoassay (CIA) is the most sensitive with a detection limit of 1.5 benzo[a]pyrene-deoxyguanosine (dG) adducts per 109 nt (10). A novel approach to quantify PAH–DNA adducts in nuclei uses an automated cellular imaging system (ACIS) which can be applied for human biomonitoring studies (11). Peter B.Farmer (Biocentre Leicester, UK; ‘Alternative approaches to 32P-postlabelling for the detection of low levels of DNA adducts’) and Karen Brown (University of Leicester, UK; ‘Accelerator mass spectrometry for DNA adduct detection’) reported on methods for DNA adduct detection by MS. Recently the sensitivity of mass spectrometric techniques, which have the ability to give more structural information than other methods, has improved to a level approaching that of 32P-postlabelling (12,13). Thus liquid chromatography-tandem mass spectrometry (LC-MS/MS) using electrospray ionization and selected monitoring has been used to determine a number of adducted deoxynucleotides in DNA, for example the benzo[a]pyrene adduct formed with the N2-position of dG using a stable isotope-labelled internal standard, with a sensitivity of three adducts per 108 nt (14). Adducts with dG appear to have a common collision-induced MS/MS fragmentation, loss of m/z 116, which allows for screening for these adducts by a technique termed ‘adductomics’ (15). Accelerator mass spectrometry (AMS) is the most sensitive method of all adduct determination techniques (1 adduct/1012 nt), however, the adduct must carry a 14C- or a 3H-label (16,17). AMS has been used to study adduct formation by heterocyclic amines (e.g. PhIP, MeIQx) and benzo[a]pyrene following administration of dietary or environmentally relevant doses to humans. This method can be capable of detecting DNA binding of extremely low levels of a single 14C-labelled therapeutic dose of a drug injected prior to surgery to humans (18). New 14C-postlabelling approaches, which exploit the sensitivity of AMS but without the need to administer a radiolabelled compound, were presented. Oliver J.Schmitz (University of Wuppertal, Germany) presented improvements for the ‘Determination of the DNA methylation level with capillary electrophoresis-laser-induced fluorescence’. This method involves hydrolysis of DNA, fluorescence labelling of modified and unmodified nucleotides, micellar electrokinetic chromatography, and laser-induced-fluorescence detection (CE-LIF) with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionylethylenediamine (BODIPY FL EDA) as the fluorescence marker (19−21). A novel sample preparation to eliminate surplus fluorescent marker resulted in an increased sample throughput. Also a new detector system based on an Ar-ion laser with a spectrometer and a CCD camera yielded a detection limit of 5 pM for BODIPY allowing the determination of DNA modifications at a concentration 10-fold lower than with commercially available CE-LIF systems. The role of aristolochic acid in the aetiology of human cancers was discussed by Arthur P.Grollman (State University of New York at Stony Brook, USA) and Heinz H.Schmeiser (German Cancer Research Center, Germany). Aristolochic acid the ingredient of Aristolochia species represents one of the few carcinogens of which the relationship between DNA adducts formation and human cancer has been defined (22). Aristolochic acid-specific DNA adducts were found in kidneys and ureters of patients who took a herbal weight-loss product in Belgium, developed aristolochic acid nephropathy (AAN) and have a high risk of urothelial cancer (23). The predominant DNA adduct formed in vivo is 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AAI), which is a premutagenic lesion leading to AT→TA transversions (24). This mutation is found in high frequency in codon 61 of the H-ras oncogene in tumours of rodents induced by AAI, suggesting that dA-AAI might be the critical lesion in the carcinogenic process in rodents. Interestingly, in an AAN patient the identical AT→TA transversion mutation was found in the p53 gene in urothelial tumour cells (25). Another nephropathy with similar pathological features is Balkan endemic nephropathy (BEN) which affects inhabitants of rural areas of the Balkans and has a strong association with upper urothelial cancer. The detection of aristolochic acid-specific DNA adducts in the renal cortex of BEN patients as well as AT→TA transversion mutations in urothelial tumours of some BEN patients support the hypothesis that chronic dietary ingestion of aristolochic acid, from bread baked with flour contaminated with Aristolochia seeds, is a risk factor in BEN and its associated cancer (26). Monica Hollstein (German Cancer Research Center, Germany) delivered a talk entitled ‘In vitro cell immortalization selects for p53 gene mutations found in human cancers’. Inactivating point mutations in the p53 tumour suppressor gene are a driving event in the immortalization of murine embryonic fibroblasts (MEFs) in vitro and can thus serve as a natural method to select for p53 mutant mouse cells (27). Immortalized cell lines arising from primary MEFs harbouring human p53 sequences (Hupki, human p53 knock-in) after treatment with carcinogens revealed mutations that match p53 mutations in human tumours (28,29). Several mutations in immortalized MEFs from cells exposed to aristolochic acid carried AT→TA transversion mutations in the human p53 gene (28,30), identical to the mutation type found in the p53 gene in urothelial tumours of AAN patients (25). Volker M.Arlt (Institute of Cancer Research, UK) discussed ‘The potential use of DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in human biomonitoring’. The lung carcinogen 3-nitrobenzanthrone is a strong genotoxic agent forming DNA adducts in vitro and in vivo after reductive activation (8,31,32). The major adducts were characterized and were persistent in several organs of the rat after intratracheal instillation. The most persistent adduct was 2-(2′-deoxyguanosin-N2-yl)-3-aminobenzanthrone (dG-N2-ABA) which was detectable by TLC 32P-postlabelling in the blood 20 weeks after treatment indicating a useful biomarker for human respiratory exposure to 3-NBA (33,34). Urine has been used to determine biomarkers of internal dose, although in some cases the measurement of a metabolite in urine may only reflect short-term exposure of a few hours (35). Similarly, some DNA adducts are excreted in urine after repair, which may represent exposure to a carcinogen over the previous 1–2 days. Jagadeesan Nair (German Cancer Research Center, Germany) presented a ‘Novel 32P-postlabelling method for the determination of adducted deoxynucleosides in human body fluids’. Etheno–DNA adducts (e.g. 1,N6-ethenodeoxyadenosine, 3,N4-ethenodeoxycytidine) are generated from exogenous carcinogens such as vinyl chloride, urethane and also from oxidative stress/lipid peroxidation products such as trans-4-hydroxy-2-nonenal (36). A new ultrasensitive 32P-postlabelling/TLC method for the analysis of 3,N4-ethenodeoxycytidine (ɛdC) as deoxynucleoside in human urine was developed (37). Using the deoxyribonucleoside kinase from Drosophila (Dm-dNK) to label nucleosides with 32P, ɛdC was determined in human urine and pancreatic juice. The absolute sensitivity of the method was 0.1 fmol ɛdC detectable in 500 μl of human urine. Dan Segerbäck (Karolinska Institute, Sweden) discussed ‘32P-postlabelling analysis of UV-induced pyrimidine dimers from human skin and urine’. Excised skin biopsies from human volunteers after UV exposure were analysed for UV dimers by a sensitive 32P-HPLC method (38). After exposure simulating 1 h of sun bathing high levels of dimers were obtained but with large individual differences. A 32P-postlabelling method for the detection of UV dimers in human urine showed a correlation between the applied dose and excreted dimers (39). Albrecht Seidel (Biochemical Institute for Environmental Carcinogens, Germany) reported on ‘Determination of urinary excreted PAH metabolites as a non-invasive human biomonitoring method’. Because metabolites of PAHs with high molecular weights are excreted in very small amounts in urine, phenols of naphthalene, pyrene and phenanthrene can be used as biomarkers of PAH exposure and determined by HPLC and gas chromatography GC/MS methodologies in the general population and in occupational settings (35,40,41). Phenanthrene tetrol appears to be a sensitive biomarker of PAH exposure even at low levels and demonstrates a good dose–response relationship. In addition, its formation reflects an important metabolic activation pathway of PAHs. The various types of phenanthrene metabolites (phenols, dihydrodiols and phenanthrene tetrol) can be used in future studies for the phenotyping of individuals to determine their possible susceptibility to develop cancer upon exposure to PAH mixtures. Panagiotis Georgiadis (National Hellenic Research Foundation, Greece) described ‘Progress towards the development of high-throughput immunochemical assays for DNA damage and repair’. There is a need for sensitive high-throughput methods to assay DNA damage and repair. The repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is important both for studies on environmental carcinogenesis by methylating carcinogens (e.g. nitrosamines) and for monitoring the susceptibility of cancer patients to the therapeutic effects of methylating cytostatic drugs (42). The activity of MGMT was assayed in cell extracts by a sensitive (limit of detection: 0.5 fmol MGMT protein) and automatable ELISA method using O6-benzylguanine as substrate. A new approach to detect and quantify different DNA adducts by ELISA using anti-adduct antibodies and anti-DNA antibodies was introduced. Hansruedi Glatt (German Institute of Human Nutrition, Germany) reported on the ‘Formation of DNA adducts in humans and laboratory animals by phytochemicals from common vegetables and fruits’. Using 32P-postlabelling DNA adducts were observed in plant DNA after homogenisation of various raw vegetables. Adduct patterns obtained from these homogenates or extracts were similar between phylogenetically related species and the homogenates were mutagenic in bacterial and mammalian test systems. In humans chewing raw broccoli plant-specific DNA adducts were detected in oral cells and at lower levels also in blood, indicating that plants release genotoxic compounds upon being damaged. Several presentations focused on DNA adduct formation by drugs. Matilde M.Marques (Technical University of Lisbon, Portugal) discussed ‘Tamoxifen and tamoxifen analogues: activation to DNA adducts in vitro and in vivo’. Tamoxifen is used as an adjuvant chemotherapeutic and as a chemopreventive agent, however, increases the risk of endometrial cancer in women (43). Thus, less genotoxic tamoxifen analogues could be advantageous in the therapeutic setting. Activated forms of such analogues were synthesised and 32P-postlabelling analyses in rats revealed lower or no DNA adduct forming potential. Marie Stiborova (Charles University Prague, Czech Republic) reported on the ‘CYP- and peroxidase-mediated formation of covalent DNA adducts by an anticancer drug ellipticine—a novel mechanism of ellipticine action’. Using 32P-postlabelling it was shown that the antineoplastic drug ellipticine is activated by CYPs and peroxidases to form DNA adducts in target tissues in rats (44−46). Metabolites of ellipticine generated by the activation with CYPs and peroxidases were identified which allows her to propose a molecular mechanism of DNA adduct formation by ellipticine. Jan Topinka (Institute of Experimental Medicine AS, Czech Republic) considered the ‘Use of DNA adduct analysis to study mechanisms of drug genotoxicity-example cyproterone acetate (CPA)’. Mechanistic studies on cyproterone acetate (CPA) revealed the induction of high levels of persistent DNA adducts in rat hepatocytes mediated by keto-reductases and sulfotransferases, although basic tests for genotoxicity were negative. CPA–DNA adducts induced in the liver can be fixed as point mutations in the target tissue of carcinogenesis but the contraceptive dose of CPA does not represent a significant cancer risk (47,48). Erwin Eder (University of Würzburg, Germany) reported on ‘Early markers in the development of colorectal tumours in the rat: DNA adducts compared with isoprostanes, histological and morphological alterations in the early stage’. The impact of chemopreventive compounds on the development of colon cancer induced by dextrane sulphate in rats was studied. Early markers of DNA damage and cancer initiation including 1,N2-propano-deoxyguanosine adducts of the lipid peroxidation product 4-hydroxy-2-nonenal (HNE-dGp) (49) were compared with morphological changes and the development of polyps and carcinoma. Using a special 32P-postlabelling method for HNE-dGp adducts dextrane sulphate-treated rats showed increased adduct levels after different time points in accordance with other early markers like inflammation. Elmar Richter (University of Munich, Germany) reported on ‘Sources of adducts releasing 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) from DNA and haemoglobin in humans’. Determination of metabolites of the tobacco-specific nitrosamines (TSNA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN) in urine showed that smokers take up 100-fold higher amounts of TSNA than non-smokers (50,51). However, using GC/MS an only 6-fold higher level of HPB-releasing DNA adducts were detected in the lung of smoking compared to non-smoking lung cancer patients. In sudden death victims the differences in adduct levels in the lung between smokers and non-smokers were even smaller. A source of tobacco-independent HPB-releasing adducts is myosmine, which occurs in edible plants and has been found in human plasma and saliva in the ng/ml range, indicating daily uptake of mg amounts (52). Two presentations focused on DNA adduct formation as a marker of cancer risk in molecular epidemiology. Roger W.Godschalk (University of Maastricht, The Netherlands) considered ‘The use of DNA adducts in surrogate tissues: pitfalls and opportunities’. In molecular epidemiological studies DNA adduct measurements have predominantly been performed in white blood cells (WBC) or broncho-alveolar lavages (BAL) (53,54). WBC consists of three subpopulations, with lymphocytes showing higher more persistent adduct levels than monocytes or granulocytes after PAH exposure. Overall assessment of DNA adducts in total WBC instead of isolated subpopulations or BAL-cells without prior characterization of the cells can attenuate the relationship between adduct levels and carcinogen exposure. Marco Peluso (Tuscany Cancer Institute, Italy) discussed ‘32P-postlabelling DNA adducts and lung cancer risk in Gen-Air, a case–control study nested in the EPIC investigation’. In this study DNA adducts were investigated prospectively for their ability to predict cancer in non-smokers in 10 European countries. Cases included lung cancer (N = 115), upper respiratory cancers (pharynx larynax; N = 82), bladder cancer (N = 124), leukaemia (N = 166) and chronic obstructive pulmonary disease or emphysema deaths (N = 77) (55). Adducts measured by 32P-postlabelling in leukocyte DNA were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88–3.93] when comparing detectable versus non-detectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06–15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24–13.88). A positive association was found between DNA adducts and ozone concentration. Wolfgang Pfau (GAB-Consulting; Germany) discussed ‘Dietary DNA adducts: heterocyclic amines and pesticides’. Diet is influencing human cancer risk. Dietary residues of plant protection products (PPP) have been considered as contributing factors, however, no association of DNA damage with dietary intake of PPPs have been reported. Heterocyclic aromatic amines (HCAs), derived from frying meat are genotoxic, form DNA adducts and are carcinogenic to rodents (56,57). HCA-derived DNA adducts in human tissues have been identified only in a few studies using 32P-postlabelling, immunochemical or mass spectrometric methods. Case–control studies confirmed the association between high dietary intake of HCAs and increased human cancer risk. Werner Lutz (University of Würzburg, Germany) discussed the ‘Correlation of DNA adducts with other endpoints of genotoxicity in mouse lymphoma cells treated with methyl methanesulfonate’. The biological significance of DNA adducts as a risk factor for mutation and cancer risk was investigated by relating increments of DNA adduct levels from an exogenous source to increments in other endpoints of genotoxicity. Mouse lymphoma cells were treated with different doses of methyl methanesulfonate (58) and O6-methyl-2′-deoxyguanosine (O6-mdGuo), 7-methylguanine (7mG), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 1,N6-etheno-2′-deoxyadenosine (ɛdAdo) were measured by LC-MS/MS in DNA. Aliquots of the cell suspension were used to perform the comet assay, micronucleus test and the thymindine kinase tk+− gene mutation assay. The results indicated that determination of DNA adduct formation may lead to a many-fold overestimation of the relevance of DNA adducts for the subsequent biological endpoints. In the symposium in honour of Prof. Manfred Wiessler, Gerhard Eisenbrand (University of Kaiserslautern, Germany) described his achievements in the chemical synthesis of active intermediates in the activation and detoxication pathways of carcinogenic N-nitrosamines. Prof Wiessler's more recent work was focused on targeting therapeutic agents to the tumour by conjugation to saccharides. As an example of new developments in targeted tumour therapy, Christopher J.Michejda (National Cancer Institute Frederick, USA) described the ‘Replication control in tumor cells as a target for DNA-interacting anti-tumor agents’. HKH40A, 2-(3-{4-[3-(8-methoxy-6-oxo-6H-2,10b-diaza-aceanthrylen-5-ylamino)-propyl]-piperazin-1-yl}-propyl)-5-nitro-benzo[de]isoquinoline-1,3-dione, and its des-methoxy analogue WMC79, are synthetic agents with potent activity against gastrointestinal and haematopoietic tumours (59). Both compounds kill cells by inducing apoptosis, by different mechanisms in cells expressing p53 and in p53 knock-out cell lines. HKH40A is more active in vivo and in vitro and has a longer plasma half-life than WMC79. The currently best therapeutic agent against pancreatic cancer is gemcitabine, to which, however, tumour cells develop resistance by up-regulation of ribonucleotide kinases. HKH40A effectively down-regulates these enzymes and a combination therapy of a human pancreatic cancer xenograft on nude (nu/nu) mice inhibited tumour growth significantly better than either agent alone. All oral and poster abstracts can be found online at http://www.swan.ac.uk/cget/ejgt/issues.htm. The meeting was sponsored by the Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) EU Network of Excellence, the German Environmental Mutagen Society (GUM) and the German Cancer Research Center (DKFZ). We are most grateful for the financial support of Novartis Pharma AG (Basel, Switzlerland), Merck KGaA (Darmstadt, Germany), Roche Diagnostics GmbH (Mannheim, Germany), Schering AG (Berlin, Germany), Altana Pharma AG (Hamburg, Germany), BASF AG (Ludwigshafen, Germany) and Boehringer-Ingelheim GmbH (Ingelheim, Germany). We thank the United Kingdom Environmental Mutagen Society (UKEMS) for providing student travel grants. The authors also wish to acknowledge the contribution made by participants to the preparation of this article through the provision of abstracts to the workshop. All oral and poster abstracts have been published online by the European Journal of Molecular and Genetic Toxicology. 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TI - ECNIS-sponsored workshop on biomarkers of exposure and cancer risk: DNA damage and DNA adduct detection and 6th GUM-32P-postlabelling workshop, German Cancer Research Center, Heidelberg, Germany, 29–30 September 2006
JF - Mutagenesis
DO - 10.1093/mutage/gel063
DA - 2007-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/ecnis-sponsored-workshop-on-biomarkers-of-exposure-and-cancer-risk-dna-x20JrxTuev
SP - 83
EP - 88
VL - 22
IS - 1
DP - DeepDyve
ER -