Toxicology and Epigenetics

Preface xxi Acknowledgment xxiii List of Contributors xxv 1 Introduction 1 Saura C. Sahu References 2 2 Environment, Epigenetics, and Diseases 5 Robert Y.S. Cheng and Wan-yee Tang 2.1 Perceptions of epigenetics 5 2.2 Environmental epigenetics and human diseases 8 2.3 Implications of environmental epigenetics and future prospects 16 2.4 Key questions to be answered 17 Acknowledgments 17 References 17 3 DNA Methylation and Toxicogenomics 25 Deepti Deobagkar and Dileep Deobagkar 3.1 Introduction 25 3.2 Toxicology 26 3.3 Toxicogenomics 27 3.4 Epigenetics 29 3.5 DNA methylation 30 3.6 DNA methyltransferases 34 3.7 Techniques of methylation detection 34 3.8 Toxicogenomics and epigenetics 40 3.9 Hydroxymethyl cytosine and toxicogenomics 42 3.10 MicroRNAs 42 3.11 DNA methylation in cancer 42 3.12 Bioinformatics approach 44 3.13 Summary 45 Acknowledgements 46 References 46 4 Chromatin at the Intersection of Disease and Therapy 51 Delphine Qu 4.1 Epigenetic marks on chromatin: a complex pathway with high flexibility 51 4.3 Epigenetic modifications and potential therapy in other diseases 60 4.4 Conclusion 66 References 66 5 Molecular Epigenetic Changes Caused by Environmental Pollutants 73 Solange S. Lewis, Gregory J. Weber, Jennifer L. Freeman, and Maria S. Sepulveda 5.1 Introduction 73 5.2 DNA methylation 75 5.3 Histone modifications 75 5.4 Small non-coding RNAs 76 5.5 Epigenetic assays 76 5.6 Bisphenol A (BPA) 78 5.7 Dichlorodiphenyltrichloroethane (DDT) 83 5.8 Dioxin (TCDD or 2,3,7,8-tetrachlorodibenzo-p-dioxin) 84 5.9 17 5.10 Hexabromocyclododecane (HBCD) 85 5.11 Methoxychlor 86 5.12 Mixture of polychlorinated biphenyls, methyl mercury, and organochlorine pesticides 87 5.13 Polybrominated diphenyl ethers (PBDEs) 88 5.14 Phthalate (di-2-ethylhexyl phthalate or DEHP) 88 5.15 Vinclozolin 88 5.16 Epigenetic changes induced by metals 90 5.17 Concluding remarks 101 References 102 6 Epigenetic Mediation of Environmental Exposures to Polycyclic Aromatic Hydrocarbons 111 Bekim Sadikovic and David I. Rodenhiser 6.1 Introduction 111 6.2 Epigenetic modifications: DNA methylation 112 6.3 DNA methylation and cancer 113 6.4 Epigenetic histone modifications 114 6.5 Benzo(a)pyrene--a prototype PAH and environmental carcinogen 115 6.6 Molecular mechanisms of benzopyrene carcinogenicity: geno- and epigeno-toxicity 115 6.7 Epigenetic effects of multiple/synergistic carcinogen exposures 120 6.8 Summary and future considerations 122 Acknowledgements 123 References 123 7 Epigenomic Actions of Environmental Arsenicals 129 Paul L. Severson and Bernard W. Futscher 7.1 Introduction 129 7.2 Arsenicals in relation to human health 130 7.3 Arsenical mechanisms of action 131 7.4 Models to study arsenical action 133 7.5 Models used to study epigenetic action 134 7.6 Epigenetic effects of arsenicals 135 7.7 Perspectives 140 References 141 8 Arsenic-Induced Changes to the Epigenome 149 Kathryn A. Bailey and Rebecca C. Fry 8.1 Introduction 149 8.2 Arsenic exposure and DNA methylation 152 8.3 DNA methylation changes associated with arsenic exposure 168 8.4 Histone modifications associated with arsenic exposure 178 8.5 MicroRNA (miRNA) alterations associated with arsenic exposure 181 8.6 Conclusions and future directions 182 Acknowledgments 183 References 183 9 Environmental Epigenetics, Asthma, and Allergy: Our Environment's Molecular Footprints 191 Stephanie Lovinsky-Desir and Rachel L. Miller 9.1 Introduction 191 9.2 Asthma environmental toxicants associated with epigenetic regulation 193 9.3 Epigenetic changes and asthma phenotype 197 9.4 'Pharmacoepigenetics' 200 9.5 Conclusion 200 References 201 10 miRNAs in Human Prostate Cancer 205 Ernest K. Amankwah and Jong Y. Park 10.1 Introduction 205 10.2 Biogenesis, function, and target of miRNA 206 10.3 miRNA and human cancer 208 10.4 miRNAs as oncogenes and tumor suppressors 209 10.5 Expression profile of miRNA in prostate cancer 210 10.6 miRNA as therapeutic targets for prostate cancer 213 10.7 Conclusion and future directions 213 References 213 11 Environment, Epigenetics, and Cardiovascular Health 219 Sanjukta Ghosh and Andrea Baccarelli 11.1 Introduction 219 11.2 Epidemiological evidence of environmental factors affecting cardiovascular health 220 11.3 Cause and effect relation between environmental exposure and cardiovascular diseases 222 11.4 Cardiovascular epigenetic signatures as risk factors and biomarkers for environmental exposure 232 11.5 Conclusion 233 References 233 12 Toxicology, Epigenetics, and Autoimmunity 241 Craig A. Cooney and Kathleen M. Gilbert 12.1 Introduction 241 12.2 Drugs and toxicants in epigenetics 243 12.3 Metabolic requirements for epigenetics 244 12.4 Autoimmunity and epigenetics 245 12.5 Conclusion 251 References 252 13 Toxicoepigenomics in Lupus 261 Donna Ray and Bruce Richardson 13.1 Introduction 261 13.2 Etiology of lupus 262 13.3 Epigenetics and lupus 264 13.4 Environmental contributions to lupus 267 13.5 Summary 270 References 270 14 Ocular Epigenomics: Potential Sites of Environmental Impact in Development and Disease 275 Kenneth P. Mitton 14.1 Introduction 275 14.2 Gene expression in ocular development 277 14.3 Epigenetic regulation in ocular development 280 14.4 DNA-methylation changes in ocular disease 283 14.5 Inherited and age-related diseases of the eye 286 14.5.1 Genetic diseases 286 14.5.2 Diabetes: metabolic memory 287 14.5.3 Spinocerebellar ataxia type 7 (SCA7): histone acetylation 287 14.6 Pharmacological effects on retinal function 287 14.7 Future research 289 References 289 15 Nuclear RNA Silencing and Related Phenomena in Animals 297 Radek Malik and Petr Svoboda 15.1 Introduction 297 15.2 Conclusion 310 Acknowledgments 310 References 310 16 Epigenetic Biomarkers in Cancer Detection and Diagnosis 317 Ashley G. Rivenbark and William B. Coleman 16.1 DNA methylation 317 16.2 Epigenetics of cancer 319 16.3 Epigenetic biomarkers for cancer diagnostics: DNA methylation 320 16.4 Application of aberrant DNA methylation to cancer diagnostics 323 16.5 Epigenetic biomarkers in breast cancer 323 16.6 Epigenetic biomarkers in prostate cancer 324 16.7 Epigenetic biomarkers in lung cancer 325 16.8 Epigenetic biomarkers in colorectal cancer 326 16.9 Epigenetic biomarkers in liver cancer 328 16.10 Cancer detection and diagnosis 330 References 332 17 Epigenetic Histone Changes in the Toxicologic Mode of Action of Arsenic 339 John F. Reichard and Alvaro Puga 17.1 Introduction 339 17.2 Epigenetics and cancer 340 17.3 Epigenetics effects of arsenic 341 17.4 Conclusions 348 References 350 18 Irreversible Effects of Diethylstilbestrol on Reproductive Organs and a Current Approach for Epigenetic Effects of Endocrine Disrupting Chemicals 357 Shinichi Miyagawa, Ryohei Yatsu, Tamotsu Sudo, Katsuhide Igarashi, Jun Kanno, and Taisen Iguchi 18.1 Introduction 357 18.2 Adverse effects of perinatally-exposed DES on the mouse vagina 358 18.3 MeDIP-ChIP 359 18.4 Future research needs 362 Acknowledgments 363 References 363 19 Epigenomics--Impact for Drug Safety Sciences 365 Harri Lempi Pierre Moulin, Philippe Couttet, Olivier Grenet, Jennifer Marlowe, Jonathan Moggs, and Rainen, Raphaelle Luisier, Arne Muller, Philippe Marc, David Heard, Federico Bolognani, emi Terranova 19.1 Introduction the dynamic epigenome and perturbations in disease 365 19.2 Relevance of epigenetics for toxicology 370 19.3 Toward identifying epigenetic biomarkers of drug-induced toxicity 371 19.4 Challenges of integrating epigenetic analysis into toxicity testing 373 19.5 Practical considerations 374 19.6 Bioinformatics and modeling of epigenomic data 376 19.7 Case study: identification of early mechanism and biomarkers for non-genotoxic carcinogenesis (NGC) 378 19.8 Conclusions 379 Acknowledgments 380 References 380 20 Archival Toxicoepigenetics: Molecular Analysis of Modified DNA from Preserved Tissues in Toxicology Studies 387 B. Alex Merrick 20.1 Introduction 387 20.2 Preservation of tissue: effects on protein and nucleic acids 388 20.3 Extraction of nucleic acids from fixed or embedded tissues 391 20.4 Analysis of methylated DNA for epigenetics 394 20.5 Survey of epigenetic studies using formalin preserved tissues 395 20.6 Prospects for toxicoepigenetics in preserved tissues 401 20.7 Conclusion 402 References 403 21 Nanoparticles and Toxicoepigenomics 409 Manasi P. Jain, Angela O. Choi, and Dusica Maysinger 21.1 Nanoparticles 409 21.2 Particles and the environment 410 21.3 Nanoparticles in soil 412 21.4 Nanoparticles in water 412 21.5 Nanoparticles and air 413 21.6 Nanoparticles in medicine 414 21.7 Nanotoxicology 414 21.8 Nanotoxicology in humans and experimental animals 414 21.9 Complications with nanotoxicological studies 416 21.10 Molecular mechanisms of nanoparticle toxicity and cellular defense mechanisms 417 21.11 Molecular mechanisms of nanoparticle-induced cytotoxicity 418 21.12 Nano-epigenomcs and epigenetics 419 21.13 Conclusion 421 References 422 22 Methods of Global Epigenomic Profiling 427 Michael W.Y. Chan, Zhengang Peng, Jennifer R. Chao, Yingwei Li, Matthew T. Zuzolo, and Huey-Jen L. Lin 22.1 Introduction 427 22.2 DNA methylation 428 22.3 Histone modifications and chromatin remodeling 435 22.4 Noncoding RNA 439 22.5 Summary and discussion 440 Acknowledgments 440 References 440 23 Transcriptomics: Applications in Epigenetic Toxicology 445 Pius Joseph 23.1 Introduction 445 23.2 Microarray analysis of gene expression profiles 446 23.3 Gene expression studies--challenges 453 23.4 Conclusions 456 Acknowledgments 456 Disclaimer 457 References 457 24 Carcinogenic Metals Alter Histone Tail Modifications 459 Yana Chervona and Max Costa 24.1 Introduction 459 24.2 Epigenetics and histone tail modifications 460 24.3 Arsenic 462 24.4 Nickel 463 24.5 Hexavalent chromium (Cr [VI]) 466 24.6 Cadmium 468 24.7 Summary 470 References 470 25 Prediction of Epigenetic and Stochastic Gene Expression Profiles of Late Effects after Radiation Exposure 475 Yoko Hirabayashi and Tohru Inoue 25.1 Introduction--pa...