The relationship between diet and human cancer has been the focus of an international symposium, organized by the Commission on the Evaluation of Food Safety (SKLM) of the Deutsche Forschungsgemeinschaft (DFG). It was held in Kaiserslautern in October 1998. The remarkable results which have been presented by renouned researchers are documented in this book. There is extensive evidence that diet influences the risk of developing cancer due to carginogens and anti-carcinogens in our food. Even though much remains to be understood about the mechanisms, it is now possible to draw consistent conclusions regarding the role of diet, obesity, and alcohol in the etiology of cancer, and to make public health recommendations on the basis of those conclusions. This symposium volume not only provides an overview of our current knowledge on this topic but also points to obvious gaps, it also presents conclusions and recommendations by the SKLM. Thus the SKLM is making available an up-to-date, scientifically substantiated source of information for a wide range of readers and users.
Preface xix I Hauptschlussfolgerungen und Empfehlungen 1(8) Einleitung 1(1) Krebs und Ernahrung: Ein multifaktorieller Zusammenhang 2(1) Carcinogene Faktoren 3(1) Anticarcinogene Faktoren 4(1) Erkenntnislucken 5(1) Empfehlungen zum Forschungsbedarf 6(3) II Main Conclusions and Recommendations 9(6) Introduction 9(1) Cancer and Food: A Multifactorial Relationship 10(1) Carcinogenic Factors 10(2) Anticarcinogenic Factors 12(1) Gaps in our Knowledge 13(1) Recommendations for Further Research 14(1) III Contributions 15(1) A General Session 15(86) Foods, Phytochemicals, and Metabolism: Anticarcinogens and Carcinogens 15(8) John D. Potter Julie A. Ross Abstract 15(1) Introduction 15(1) Vegetables, fruit, and cancer 16(4) Adult cancers 16(2) Infant leukemia 18(1) Implications 19(1) Obesity and cancer 20(1) Breast cancer 20(1) Colon cancer 20(1) Implications 20(1) Summary 21(2) Evidence from Migrant Studies for Dietary Effects on Cancer Incidence and Mortality 23(10) Margaret McCredie Abstract 23(1) Introduction 24(1) Characteristics of migrant studies 24(1) Examples from incidence and mortality rates of cancer at selected sites 25(2) Colorectal cancer 25(1) Stomach cancer 26(1) Liver cancer 26(1) Breast cancer 27(1) Prostate cancer 27(1) The effect of migration on diet 27(1) Are dietary factors implicated? 28(2) Genetic susceptibility 30(1) Conclusion 30(3) Caloric Intake as a Modulator of Carcinogenicity and Anti-carcinogenicity 33(42) Ronald W. Hart T. Bucci J. Seng A. Turturro J. E. A. Leakey R. Feuers P. Duffy J. James B. Lyn-Cook J. Pipkin S. Y. Li Abstract 33(1) Introduction 34(1) Relationship of body weight to cancer 35(1) Homeostasis 36(4) Physiological effects 36(1) Drug metabolism 37(1) Direct effects 37(1) Age-related effects 37(1) Circadian effects 38(1) Intermediary metabolism 38(1) Genetic effects 39(1) Evolutionary perspective 40(3) The Role of Nutritional Factors: Colon Cancer 43(32) Robert W. Owen Abstract 43(1) Introduction 44(1) Fat and bile acids 45(4) Calcium and bile acids 49(4) Fibre and bile acids 53(4) Phytic acid 57(4) Nonsteroidal anti-inflammatory drugs 61(3) Reactive oxygen species (ROS) 64(4) Conclusions 68(7) Controversies Surrounding Diet and Breast Cancer 75(18) Lenore Arab Michelle Mendez Abstract 75(1) Dietary fat, energy intakes and breast cancer 76(1) Individual fatty acids and breast cancer 77(1) EURAMIC study 78(1) Monounsaturated fats and breast cancer 79(1) Polyunsaturated fatty acids 79(2) Trans-fatty acids and breast cancer 81(1) Antioxidants and breast cancer 81(1) Cruciferous vegetables and breast cancer 82(1) Xeno-estrogens 83(3) Phyto-estrogens 84(1) Organochlorine pesticides 85(1) Alcohol 86(1) Summary and conclusion 87(6) Molecular Epidemiology: Identification of Susceptible Subgroups 93(8) Christine B. Ambrosone Abstract 93(1) Introduction 94(1) Identification of susceptible subgroups 95(1) Identification of etiologic agents in carcinogenesis 96(1) Caveat emptor! 97(2) Conclusion 99(2) B Carcinogenic Factors: Exogenous 101(127) Relative Contributions of Chemical Carcinogens in the Diet vs Overnutrition - The Role of Individual Dose and Susceptibility 101(7) Werner K. Lutz Josef Schlatter Abstract 101(1) Chemical carcinogens in the diet vs overnutrition 102(1) Individual dietary habits resulting in high dose levels 103(1) Synergistic effects of exposure to other carcinogens 104(1) Anticarcinogenicity of dietary factors 105(1) J-shaped dose response for tumor induction: Caffeic acid 105(2) Conclusions 107(1) Alcohol and Cancer 108(30) Helmut K. Seitz Nils Homann Abstract 108(1) Introduction 109(1) Epidemiology and experimental carcinogenesis 109(7) Upper alimentary tract 109(2) Liver 111(1) Large intestine 112(3) Breast 115(1) Other organs 115(1) General mechanisms by which alcohol modulates carcinogenesis 116(11) Sources of carcinogen intake 116(2) Ethanol metabolism and its link to carcinogenesis 118(1) Generation of acetaldehyde via ADH and by gastrointestinal bacteria 118(1) Induction of cytochrome P450 2E1 and production of free radicals 119(1) Enhanced CYP 2E1-mediated procarcinogen activation 120(3) Effect of alcohol on DNA 123(1) The effect of ethanol on cell regeneration and its link to carcinogenesis 123(2) Alcohol-associated nutritional deficiencies and carcinogenesis 125(2) Specific pathogenesis of alcohol-associated organ cancer 127(11) Upper alimentary tract 127(1) Liver 127(2) Large intestine 129(1) Breast 130(8) Heterocyclic Aromatic Amines: Genotoxicity and DNA Adduct Formation 138(30) Wolfgang Pfau Abstract 138(1) Introduction 139(1) Levels 140(2) Adducts 142(4) Mutagenicity of adducts 146(2) Genotoxic effects 148(4) Carcinogenic activity 152(1) Mixture effects 153(2) Conclusions 155(13) Heterocyclic Aromatic Amines: Genetic Susceptibility 168(12) Montserrat Garcia-Closas Rashmi Sinha Abstract 168(1) Introduction 169(1) Heterocyclic aromatic amines and cancer in human populations 170(3) Exposure assessment of HCAs in epidemiologic studies 170(2) Cancer risk and HCA intake in human populations 172(1) Studies of meat intake and risk of cancer 172(1) Genetic susceptibility to heterocyclic aromatic amines 173(3) Polymorphisms for heterocyclic amine metabolism in humans 173(2) Epidemiologic studies on metabolic polymorphisms, meat/HCA intake and cancer risk 175(1) Colorectal adenomas and cancer 175(1) Bladder cancer 176(1) Breast cancer 176(1) Limitations and future directions 176(4) A Review of Recent Advances in the Genotoxicity of Carcinogenic Mycotoxins 180(25) Guy Dirheimer Abstract 180(1) Introduction 181(1) Aflatoxins 181(4) Sterigmatocystin (STC) 185(1) Ochratoxin A (OTA) 186(3) Citrinin 189(1) Zearalenone 190(2) Patulin 192(1) Trichothecenes 193(1) Fumonisins 194(1) Fusarin C 195(1) Griseofulvin 195(1) Conclusion 196(9) The Role of Nitrosation: Exogenous vs Endogenous Exposure to N-Nitroso Compounds 205(11) David E. G. Shuker Abstract 205(1) Introduction 206(1) Exogenous exposures to NOC 207(1) Endogenous synthesis of NOC 208(1) Alkyl-DNA adducts as indicators of NOC exposure 209(1) Nitrosation of glycine and other amino acids as a source of endogenous DNA damage 210(3) Conclusions 213(3) Meat, Other Dietary Factors and Intestinal Ammonia and N-Nitro Compound Formation in Relation to Colorectal Cancer 216(12) Sheila A. Bingham Abstract 216(1) Introduction 217(1) Epidemiology of diet and colorectal cancer 218(1) Starch, non starch polysaccharides and fermentation 219(2) Meat and nitrogen metabolism in the colon 221(2) Conclusion 223(5) C Carcinogenic Factors: Endogenous 228(28) DNA Damage by Nitrogen and Oxygen Free Radicals and its Modulation by Dietary Constituents 228(6) Steven R. Tannenbaum Abstract 228(1) Chemistry of nitric oxide 229(1) Nitric oxide-induced DNA damage via the N2O3 pathway 229(2) DNA damage from peroxynitrite 231(1) NO-induced mutagenesis 232(2) Oxidative DNA Damage and its Cellular Consequences 234(11) Bernd Epe D. Ballmaier O. Will S. Hollenbach H.-C. Mahler M. I. Homburg J. P. Radicella Abstract 234(1) Introduction 235(1) Steady-state levels of oxidative DNA modifications in mammalian cells 236(2) Factors that influence the steady-state levels of oxidative DNA damage 238(1) Mutagenicity associated with oxidative DNA damage 239(2) Conclusions 241(4) Fermentation Profiles in the Gut and Functional Effects of Food Components 245(11) Wolfgang Scheppach Abstract 245(1) Introduction 245(1) Colonic SCFA concentrations and carcinogenesis 246(1) SCFAs and proliferation of normal colonocytes 247(1) Butyrate and colonic ``hyperproliferation 248(1) Butyrate and adenoma cell lines 248(1) Butyrate, propionate, and proliferation of colon cancer cell lines 249(1) Butyrate and markers of differentiation 249(1) Effect of butyrate on histones 250(1) Effects of butyrate on gene expression 251(1) Butyrate and tumor invasiveness 252(1) Butyrate as a treatment for metastatic cancer in experimental animals 252(1) Conclusion 253(3) D Anticarcinogenic Factors 256(140) Involvement of Free Radicals in Carcinogenesis and Modulation by Antioxidants 256(11) Anthony T. Diplock† Abstract 256(1) Introduction 257(1) Free radical generation and DNA as target for attack 257(2) Lipid peroxidation and carcinogenesis 259(2) Modulation by dietary antioxidants of free radical attack: epidemiological studies 261(3) Enhancement of antioxidant intake and safety 264(3) Anticarcinogenic Factors in Plant Foods and Novel Techniques to Elucidate Their Potential Chemopreventive Activities 267(27) Beatrix L. Pool-Zobel Abstract 267(1) Introduction 268(1) Mechanisms of carcinogenesis 268(4) The concept of chemoprevention/dietary prevention 272(1) Phytoprotectants 273(7) Mechanisms of protective activities 280(6) Antigenotoxic activities 281(1) Antioxidative activities 282(1) Induction of chemopreventive enzymes 283(1) Antiproliferative activity 284(1) Induction of apoptosis 285(1) Modulation of biomarkers 285(1) Conclusions 286(8) Carotenoids and Anthocyans 294(12) Gerhard Rechkemmer Abstract 294(2) Introduction 296(1) Carotenoids 296(5) Evidence for anticarcinogenic activity of carotenoids 298(1) β-Carotene 298(2) ATBC 300(1) CARET 300(1) Conclusions from ATBC and CARET 300(1) Lycopene 300(1) Other carotenoids 301(1) Anthocyanins 301(5) Experimental evidence for anticarcinogenic activity of anthocyanins 302(4) Anticarcinogenesis by Isothiocyanates, Indole-3-carbinol, and Allium Thiols 306(28) Stephen S. Hecht Abstract 306(1) Isothiocyanates and glucosinolates 307(8) Occurrence and formation 307(1) Inhibition of carcinogenesis by isothiocyanates, glucosinolates, and cruciferous vegetables 308(5) Mechanisms of chemoprevention by isothiocyanates 313(2) Indole-3-carbinol 315(4) Occurrence and formation 315(1) Effects of indole-3-carbinol on carcinogenesis 316(1) Mechanisms of chemoprevention by indole-3-carbinol 317(2) Thiols of Allium plants 319(3) Occurrence and formation 319(1) Effects of Allium thiols on carcinogenesis 319(3) Mechanisms of chemoprevention by Allium thiols 322(1) Conclusions 322(12) Tea and Cancer: What Do We Know and What Do We Need to Know? 334(14) Chung S. Yang Guang-yu Yang Sungbin Kim Mao-Jung Lee Jie Liao Jee Chung Abstract 334(1) Introduction 335(1) Studies with animal models 336(2) Inhibition of lung tumorigenesis 336(1) Inhibition of skin tumorigenesis 337(1) Studies on colon and breast cancers 337(1) Epidemiological studies 338(1) Possible active components and their bioavailability 339(3) Possible active components 339(1) Absorption and tissue distribution in animals 340(1) Blood and saliva levels in humans 341(1) Possible mechanisms for the inhibitory actions of tea on tumorigenesis 342(1) Concluding remarks 343(5) Lignans and Isoflavones 348(17) Lilian U. Thompson Abstract 348(1) Introduction 348(2) Anticancer effects 350(7) Epidemiological studies 350(1) In vitro studies 351(1) Animal studies 352(1) Soybean and isoflavones 352(1) Breast cancer 352(1) Other cancers 353(1) Flaxseed and lignans 354(1) Breast cancer 354(1) Other cancers 355(1) Clinical studies 356(1) Safety 357(1) Conclusion and future research 358(7) Chemoprevention of Colon Carcinogenesis by Non-Nutritive Compounds in Foods 365(26) Takuji Tanaka Abstract 365(1) Introduction 365(7) Screening of possible chemopreventive agents against rat colon tumorigenesis ability using a 5-week short-term bioassay of ACF 372(1) Evaluation of chemopreventive ability of selected compounds using a long-term rat colon carcinogenesis model 373(1) Chemoprevention of rat colon carcinogenesis by DIO and HPD 373(3) Chemoprevention of rat colon carcinogenesis by ACA 376(4) Chemoprevention of rat colon carcinogenesis by AUR 380(5) Discussion 385(6) Chemoprevention of Intestinal Neoplasia 391(5) Henk J. van Kranen C. F. van Kreijl Abstract 391(1) Manuscript 392(4) E Biomarkers 396(23) Exocyclic DNA Adducts as Biomarkers for Oxidative Stress, Dietary Risk Factors and Cancer Chemopreventive Approaches 396(8) Helmut Bartsch J. Nair Abstract 396(1) Introduction 397(2) Results and discussion 399(5) Increased exocyclic adduct formation as a consequence of LPO 399(1) Etheno adducts 399(1) Malondialdehyde-dG and propano-dG adducts 400(1) Perspectives 400(4) Biological Markers in Chemoprevention Research 404(15) LaVerne A. Mooney Frederica P. Perera Abstract 404(1) Introduction 405(1) Validation studies 405(6) Inter- and intra-individual variation 407(1) Transitional studies: Nutritional and genetic factors and DNA damage 407(1) PAH-DNA as a marker of lung cancer risk 408(1) Nutritional status and lung cancer risk 408(2) Genetic susceptibility to carcinogen exposure 410(1) Early vs intermediate markers 411(1) Modulation of biomarkers in an antioxidant vitamin trial in smokers 412(2) Conclusions 414(5) F Diet and Cancer: Evaluation Criteria 419(10) Approaches Towards Assessment of Carcinogens/Anticarcinogens 419(1) Harri Vainio Abstract 419(1) Diet and Cancer: Public Health Aspects 420(9) Martin J. Wiseman Abstract 420(1) Introduction 420(2) Diet and cancer in the UK 422(3) The nature of associations 423(1) The epidemiological evidence 424(1) Experimental evidence 425(1) Drawing overall conclusions 425(1) Diet and cancer - conclusions 425(1) Conclusions 426(3) IV Posters 429(90) Induction of Unscheduled DNA Synthesis by the Mycotoxin Ochratoxin A in Cultured Urothelial Cells from Pigs and Humans 429(4) W. Follmann A. Dorrenhaus A. Flieger K. Golka Gisela H. Degen In vitro Covalent Binding as a Possible Quantitative Indicator for the Genotoxic Potency of Aflatoxin B1 in Rat and Human 433(5) Kerstin Groß-Steinmeyer J. Weymann H. G. Koebe M. Metzler N-Palmitoyl-HFB1: A New Metabolite of Hydrolyzed Fumonisin (HFB1) in Rat Liver Microsomes 438(3) Hans-Ulrich Humpf E.-M. Schmelz F. I. Meredith A. H. Merrill Are Nitroso Bile Acids Involved in Carcinogenesis Following Reflux of Duodenal Juice? 441(1) Martin Fein Karl-Hermann Fuchs Stefanie Diem Markus Herderich The Occurrence of Heterocyclic Aromatic Amines in Various Food Samples Analyzed by High Performance Liquid Chromatography-Electrospray Tandem Mass Spectrometry (HPLC-ESI-MS/MS) 442(3) Elke Richling Dietmar Haring Markus Herderich Peter Schreier Determination of HAAs in Samples with Strong Matrix Influences 445(3) Marc Vollenbroker K. Eichner Activation of Nitrosamines in Metabolically Proficient Cell Systems to Induce Cytotoxic and Genotoxic Effects 448(2) Monika Hofer Christine Janzowski Richard N. Loeppky Gerhard Eisenbrand 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Suppresses Apoptosis in the Livers of c-myc Transgenic Mice and in Rat Hepatocytes in Primary Culture 450(2) Wolfgang Worner Martina Muller Hans-Joachim Schmitz Dieter Schrenk Metabolism of Benzo(c)phenanthrene and Genotoxicity of the Corresponding Dihydrodiols After Activation by Human Cytochrome P450-Enzymes in Comparison to Dibenzo(a,l)pyrene-11,12-dihydrodiol and Benzo(a)pyrene-7,8-dihydrodiol 452(3) Matthias Baum Werner Kohl Steven S. Hecht Shantu Amin F. Peter Guengerich Gerhard Eisenbrand In vitro Toxicity and Microsomal Metabolism of the Polycyclic Musk Fixolide and Crysolide 455(4) Christine Janzowski Martin Burkart Aribert Vetter Gerhard Eisenbrand Special Effects of α,β-Unsaturated Aldehydes in Human Lymphocytes Studied by Premature Chromosome Condensation (PCC) 459(6) Eva Ritter Christiane Meilike Harry Scherthan Heinrich Zankl Determination of Apoptosis and Mutagenic Effects of 2-Cyclohexen-1-one in Human Leukemic Cell Lines and Peripheral Blood Lymphocytes 465(4) Anja Genzlinger I. Zimmermann C. Janzowski H. Zankl Food Relevant α,β-Unsaturated Carbonyl Compounds: In vitro Toxicity, Genotoxic (Mutagenic) Effectiveness and Reactivity Towards Glutathione 469(5) Christine Janzowski V. Glaab E. Samimi J. Schlatter B. L. Pool-Zobel G. Eisenbrand Enantioselective Metabolic Activation of Safrole 474(4) Robert Landsiedel U. Andrae A. Kuhlow M. Scholtyssek H. R. Glatt Inhibition of DNA Repair Processes by Inorganic Arsenic 478(3) Andrea Hartwig U. D. Groblinghoff Y. Hiemstra L. H. F. Mullenders Identification of Antiandrogens with Functional Transactivation in vitro Assays and Molecular Modeling Analysis 481(3) S. Guth D. Seng S. Bohm B. Mußler G. Eisenbrand Oxidative Metabolism and Genotoxicity of Enterolactone and Enterodiol 484(5) Eric Jacobs Manfred Metzler Genotoxic Potential of Isoflavone and Coumestane Phytoestrogens 489(4) S. E. Kulling Leane Lehmann S. Mayer M. Metzler Study on Mechanisms by Which Carrot and Tomato Juice May Reduce Oxidative DNA-Damages in vivo: in vitro Effects of All-trans-β-Carotene and Lycopene 493(2) B. L. Pool-Zobel Michael Glei B. Spankuch G. Rechkemmer Carotenoids and Vitamin D: Micronutrients Capable to Stimulate Gap Junctional Communication 495(4) Wilhelm Stahl S. Nicolai A. Clairmont H. Sies Protective Effects of Vitamins C and E in Smokers Monitored by Ascorbyl Radical Formation in Plasma and the Frequency of Micronuclei in Lymphocytes 499(1) Matthias Schneider Kerstin Diemer Karin Engelhart Heinrich Zankl Wolfgang E. Trommer Hans K. Biesalski Anticarcinogenic Effects of Genotoxic Carcinogens Based on Cell-Cycle Delay, Calculated for the Two-Stage Clonal Expansion Model of Carcinogenesis 500(3) Annette Kopp-Schneider W. K. Lutz Occurrence of Emodin, Chrysophanol and Physcion in Vegetables, Herbs and Liquors. Genotoxicity and Anti-Genotoxicity of the Anthraquinones and of the Whole Plants 503(4) Stefan O. Muller Marko Schmitt Wolfgang Dekant Helga Stopper Josef Schlatter Peter Schreier Werner K. Lutz Degradation of Flavonoids by the Human Intestinal Bacteria Eubacterium Ramulus and Enterococcus Casseliflavus 507(1) R. Simmering Heiko Schneider M. Blaut Distribution Kinetics of a Flavonoid Extract in the Gastrointestinum of Rats 508(4) Holger Pforte Jurg Hempel Gisela Jacobasch Flavones and Inhibition of Tumor Cell Growth: New Aspects on the Mechanism of Action 512(1) E. Niederberger Susanne Meiers A. Genzlinger H. Zankl W. C. Tang G. Eisenbrand D. Marko Food Derived Flavonoids That Affect Proliferation, Differentiation and Apoptosis in Human Colon Carcinoma Cells (HT-29) and Their Mode of Action 513(6) Uwe Wenzel Sabine Kuntz Stefan Storcksdieck Ulrike Jambor de Sousa Hannelore Daniel Attachment 519(1) List of Participants and Contributors on the Symposium of the DFG-Senate Commission on Food Safety (SKLM) ``Carcinogenic/Anticarcinogenic Factors in Food: Novel Concepts? 519
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