Skip to main content
SpringerLink
Log in

Chemical Carcinogenesis and Epigenetics

  • Chapter
  • First Online:
Chemical Carcinogenesis

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Gene expression in higher eukaryotes is controlled in part by a complex series of chemical modifications to DNA and associated histone proteins that alter the condensation of chromatin and accessibility of genes for transcription. The transcriptional silencing of tumor suppressor genes or the inappropriate activation of transforming genes is a hallmark of human tumors and, in many cases, can be attributed to the perturbation of epigenetic signals. In this review, we provide a brief introduction to epigenetic gene control with a focus on molecular events and, in particular, the role of 5-methylcytosine (5mC) in DNA on epigenetic programming. The mechanisms by which enzymatic methylation alters DNA–protein interactions and methylase activity are described. The conversion of cytosine to 5mC changes the chemistry of the base and, in some cases, the surrounding DNA as well. We describe how carcinogens can modify epigenetic patterns through chemical interactions with cytosine and 5mC. Emerging evidence also suggests that chemical damage to DNA can alter interactions with methyltransferases and proteins containing a methyl-binding domain, resulting in heritable changes in epigenetic signals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 229.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alegria AH (1967) Hydroxymethylation of pyrimidine mononucleotides with formaldehyde. Biochem Biophys Acta 149:317–324

    PubMed  CAS  Google Scholar 

  • Allaman-Pillet N, Djemai A, Bonny C, Schroderet DF (1998) Methylation status of CpG sites and methyl-CpG binding proteins are involved in the promoter regulation of the mouse Xist gene. Gene Expr 7:61–73

    PubMed  CAS  Google Scholar 

  • Baltz RH, Bingham PM, Drake JW (1976) Heat mutagenesis in bacteriophage T4: the transition pathway. Proc Natl Acad Sci USA 73:1269–1273

    Article  PubMed  CAS  Google Scholar 

  • Bauerle M, Doenecke D, Albig W (2002) The requirement of H1 histones for a heterodimeric nuclear import receptor. J Biol Chem 277:32480–32489

    Article  PubMed  Google Scholar 

  • Baylin SB (2005) DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol 2 Suppl 1:S4–S11

    Article  PubMed  CAS  Google Scholar 

  • Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP (1998) Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 72:141–196

    Article  PubMed  CAS  Google Scholar 

  • Becker PB, Ruppert S, Schutz G (1987) Genomic footprinting reveals cell type-specific DNA binding of ubiquitous factors. Cell 51:435–443

    Article  PubMed  CAS  Google Scholar 

  • Bednarik DP, Duckett C, Kim SU, Perez VL, Griffis K, Guenthner PC, Folks TM (1991) DNA CpG methylation inhibits binding of NF-kappa B proteins to the HIV-1 long terminal repeat cognate DNA motifs. New Biol 3:969–976

    PubMed  CAS  Google Scholar 

  • Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M (1999) A mammalian protein with specific demethylase activity for mCpG DNA. Nature 397:579–583

    Article  PubMed  CAS  Google Scholar 

  • Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8:1499–1504

    Article  PubMed  CAS  Google Scholar 

  • Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209–213

    Article  PubMed  CAS  Google Scholar 

  • Bogdanovic O, Veenstra GJ (2009) DNA methylation and methyl-CpG binding proteins: developmental requirements and function. Chromosoma 118:549–565

    Article  PubMed  CAS  Google Scholar 

  • Boorstein RJ, Chiu LN, Teebor GW (1989) Phylogenetic evidence of a role for 5-hydroxymethyluracil-DNA glycosylase in the maintenance of 5-methylcytosine in DNA. Nucleic Acids Res 17: 7653–7661

    Article  PubMed  CAS  Google Scholar 

  • Burdzy A, Noyes KT, Valinluck V, Sowers LC (2002) Synthesis of stable-isotope enriched 5-methylpyrimidines and their use as probes of base reactivity in DNA. Nucleic Acids Res 30:4068–4074

    Article  PubMed  CAS  Google Scholar 

  • Cannon SV, Cummings A, Teebor GW (1988) 5-Hydroxymethylcytosine DNA glycosylase activity in mammalian tissue. Biochem Biophys Res Commun 151:1173–1179

    Article  PubMed  CAS  Google Scholar 

  • Caradonna S, Muller-Weeks S (2001) The nature of enzymes involved in uracil-DNA repair: isoform characteristics of proteins responsible for nuclear and mitochondrial genomic integrity. Curr Protein Pept Sci 2:335–347

    Article  PubMed  CAS  Google Scholar 

  • Carbonnaux C, Fazakerley GV, Sowers LC (1990) An NMR structural study of deaminated base pairs in DNA. Nucleic Acids Res 18:4075–4081

    Article  PubMed  CAS  Google Scholar 

  • Castro GD, Diaz Gomez MI, Castro JA (1996) 5-Methylcytosine attack by hydroxyl free radicals and during carbon tetrachloride promoted liver microsomal lipid peroxidation: structure of reaction products. Chem Biol Interact 99:289–299

    Article  PubMed  CAS  Google Scholar 

  • Cedar H, Bergman Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10:295–304

    Article  PubMed  CAS  Google Scholar 

  • Cedar H, Verdine GL (1999) Gene expression. The amazing demethylase. Nature 397:568–569

    Article  PubMed  CAS  Google Scholar 

  • Chen JX, Zheng Y, West M, Tang MS (1998) Carcinogens preferentially bind at methylated CpG in the p53 mutational hot spots. Cancer Res 58:2070–2075

    PubMed  CAS  Google Scholar 

  • Chen CS, White A, Love J, Murphy JR, Ringe D (2000) Methyl groups of thymine bases are important for nucleic acid recognition by DtxR. Biochemistry 39:10397–10407

    Article  PubMed  CAS  Google Scholar 

  • Cier A, Lefier A, Ravier M, Nofre C (1962) Action du radical libre hydroxyle sur les bases pyrimidiques (The action of free hydroxyl radicals on the pyrimidine bases). C R Hebd Seances Acad Sci 254:504–506

    CAS  Google Scholar 

  • Comb M, Goodman HM (1990) CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res 1:3975–3982

    Article  Google Scholar 

  • Cortazar D, Kunz C, Saito Y, Steinacher R, Schar P (2007) The enigmatic thymine DNA glycosylase. DNA Repair (Amst) 6:489–504

    Article  CAS  Google Scholar 

  • Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–780

    Article  PubMed  CAS  Google Scholar 

  • Darwanto A, Theruvathu JA, Sowers JL, Rogstad DK, Pascal T, Goddard W 3rd, Sowers LC (2009) Mechanisms of base selection by human single-stranded selective monofunctional uracil-DNA glycosylase. J Biol Chem 284:15835–15846

    Article  PubMed  CAS  Google Scholar 

  • Das PM, Singal R (2004) DNA methylation and cancer. J Clin Oncol 22:4632–4642

    Article  PubMed  CAS  Google Scholar 

  • Delepierre M, Langlois D’Estaintot B, Igolen J, Roques BP (1986) Conformational studies of d(m5CpGpm5CpG) and d(CpGpCpG) by 1H and 31P NMR. Eur J Biochem 161:571–577

    Article  PubMed  CAS  Google Scholar 

  • Denissenko MF, Chen JX, Tang MS, Pfeifer GP (1997) Cytosine methylation determines hot spots of DNA damage in the human p53 gene. Proc Natl Acad Sci USA. 94:3893–3898

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich M, Wang RY (1981) 5-Methylcytosine in eukaryotic DNA. Science 212:1350–1357

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich M, Norris KF, Wang RY, Kuo KC, Gehrke CW (1986) DNA cytosine methylation and heat-induced deamination. Biosci Rep 6:387–393

    Article  PubMed  CAS  Google Scholar 

  • Esteller M (2007) Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet 16 Spec No 1:R50–R59

    Google Scholar 

  • Falzon M, Kuff EL (1991) Binding of the transcription factor EBP-80 mediates the methylation response of an intracisternal A-particle long terminal repeat promoter. Mol Cell Biol 11:117–125

    PubMed  CAS  Google Scholar 

  • Flaks JG, Cohen SS (1959) Virus-induced acquisition of metabolic function. I. Enzymatic formation of 5-hydroxymethyldeoxycytidylate. J Biol Chem 234:1501–1506

    PubMed  CAS  Google Scholar 

  • Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 89:1827–1831

    Article  PubMed  CAS  Google Scholar 

  • Fujii S, Wang AH, van der Marel G, van Boom JH, Rich A (1982) Molecular structure of (m5 dC-dG)3: the role of the methyl group on 5-methyl cytosine in stabilizing Z-DNA. Nucleic Acids Res 10:7879–7892

    Article  PubMed  CAS  Google Scholar 

  • Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T (2003) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278:4035–4040

    Article  PubMed  CAS  Google Scholar 

  • Gaston K, Fried M (1995) CpG methylation has differential effects on the binding of YY1 and ETS proteins to the bi-directional promoter of the Surf-1 and Surf-2 genes. Nucleic Acids Res 23:901–909

    Article  PubMed  CAS  Google Scholar 

  • Geacintov NE, Cosman M, Hingerty BE, Amin S, Broyde S, Patel DJ (1997) NMR solution structures of stereoisometric covalent polycyclic aromatic carcinogen-DNA adduct: principles, patterns, and diversity. Chem Res Toxicol 10:111–146

    Article  PubMed  CAS  Google Scholar 

  • Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481–514

    Article  PubMed  CAS  Google Scholar 

  • Graves KL, Hardy LW (1994) Kinetic and equilibrium alpha-secondary tritium isotope effects on reactions catalyzed by dCMP hydroxymethylase from bacteriophage T4. Biochemistry 33:13049–13056

    Article  PubMed  CAS  Google Scholar 

  • Gruenbaum Y, Stein R, Cedar H, Razin A (1981) Methylation of CpG sequences in eukaryotic DNA. FEBS Lett 124:67–71

    Article  PubMed  CAS  Google Scholar 

  • Grunau G, Clark SJ, Rosenthal A (2001) Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res 29:E65

    Article  PubMed  CAS  Google Scholar 

  • Hardy TA, Baker DJ, Newman EM, Sowers LC, Goodman MF, Smith SS (1987) Size of the directing moiety at carbon 5 of cytosine and the activity of human DNA (cytosine-5) methyltransferase. Biochem Biophys Res Commun 145:146–152

    Article  PubMed  CAS  Google Scholar 

  • Hardy LW, Graves KL, Nalivaika E (1995) Electrostatic guidance of catalysis by a conserved glutamic acid in Escherichia coli dTMP synthase and bacteriophage T4 dCMP hydroxymethylase. Biochemistry 34:8422–8432

    Article  PubMed  CAS  Google Scholar 

  • Haverkamp J, Charbonneau B, Ratliff TL (2008) Prostate inflammation and its potential impact on prostate cancer: a current review. J Cell Biochem 103:1344–1353

    Article  PubMed  CAS  Google Scholar 

  • Hendrich B, Hardeland U, Ng H-H, Jiricny J, Bird A (1999) The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature 401:301–304

    Article  PubMed  CAS  Google Scholar 

  • Hermann R, Hoeveler A, Doerfler W (1989) Sequence-specific methylation in a downstream region of the late E2A promoter of adenovirus type 2 DNA prevents protein binding. J Mol Biol 210:411–415

    Article  PubMed  CAS  Google Scholar 

  • Herring JL, Rogstad DK, Sowers LC (2009) Enzymatic methylation of DNA in cultured human cells studied by stable isotope incorporation and mass spectrometry. Chem Res Toxicol 22:1060–1068

    Article  PubMed  CAS  Google Scholar 

  • Ho KL, McNae IW, Schmiedeberg L, Klose RJ, Bird AP, Walkinshaw MD (2008) MeCP2 binding to DNA depends upon hydration at methyl-CpG. Mol Cell 29:525–531

    Article  PubMed  CAS  Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  PubMed  CAS  Google Scholar 

  • Hon GC, Hawkins RD, Ren B (2009) Predictive chromatin signatures in the mammalian genome. Hum Mol Genet 18:R195–R201

    Article  PubMed  CAS  Google Scholar 

  • Hotchkiss RD (1948) The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J Biol Chem 175:315–332

    PubMed  CAS  Google Scholar 

  • Huang X, Colgate KC, Kolbanovskiy A, Amin S, Geacintov NE (2002) Conformational changes of a benzo [a]pyrene diol epoxide-N(2)-dG adduct induced by a 5’-flanking 5-methyl-substituted cytosine in a (Me)CG double-stranded oligonucleotide sequence context. Chem Res Toxicol 15:438–444

    Article  PubMed  CAS  Google Scholar 

  • Iguchi-Ariga SM, Schaffner W (1989) CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev 3:612–619

    Article  PubMed  CAS  Google Scholar 

  • Ikegami K, Ohgane J, Tanaka S, Yagi S, Shiota K (2009) Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development. Int J Dev Biol 53:203–214

    Article  PubMed  CAS  Google Scholar 

  • Ivarie R (1987) Thymine methyls and DNA-protein interactions. Nucleic Acids Res 15:9975–9983

    Article  PubMed  CAS  Google Scholar 

  • Iyer LM, Tahiliani M, Rao A, Aravind L (2009) Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle 8:1698–1710

    Article  PubMed  CAS  Google Scholar 

  • Jancso A, Botfield MC, Sowers LC, Weiss MA (1994) An altered-specificity mutation in a human POU domain demonstrates functional analogy between the POU-specific subdomain and phage lambda repressor. Proc Natl Acad Sci USA 91:3887–3891

    Article  PubMed  CAS  Google Scholar 

  • Jeltsch A (2006) Molecular enzymology of mammalian DNA methyltransferases. Curr Top Microbiol Immunol 301:203–225

    Article  PubMed  CAS  Google Scholar 

  • Jiang Q, Hurst JK (1997) Relative chlorinating, nitrating, and oxidizing capabilities of neutrophils determined with phagocytosable probes. J Biol Chem 272:32767–32772

    Article  PubMed  CAS  Google Scholar 

  • Jiang Q, Blount BC, Ames BN (2003) 5-Chlorouracil, a marker of DNA damage from hypochlorous acid during inflammation. A gas chromatography-mass spectrometry assay. J Biol Chem 278:32834–32840

    Article  PubMed  CAS  Google Scholar 

  • Kang JI Jr, Sowers LC (2008) Examination of hypochlorous acid-induced damage to cytosine residues in a CpG dinucleotide in DNA. Chem Res Toxicol 21:1211–1218

    Article  PubMed  CAS  Google Scholar 

  • Kang JI Jr, Burdzy A, Liu P, Sowers LC (2004) Synthesis and characterization of oligonucleotides containing 5-chlorocytosine. Chem Res Toxicol 17:1236–1244

    Article  PubMed  CAS  Google Scholar 

  • Kastan MB, Gowans BJ, Lieberman MW (1982) Methylation of deoxycytidine incorporated by excision-repair synthesis of DNA. Cell 30:509–516

    Article  PubMed  CAS  Google Scholar 

  • Khattak MN, Green JH (1966) Gamma-irradiation of nucleic-acid constituents in de-aerated aqueous solutions. II. 5-methyl cytosine. Int J Radiat Biol Relat Stud Phys Chem Med 11:137–143

    Article  PubMed  CAS  Google Scholar 

  • Kim JK, Samaranayake M, Pradhan S (2009) Epigenetic mechanisms in mammals. Cell Mol Life Sci 66:596–612

    Article  PubMed  CAS  Google Scholar 

  • Kovesdi I, Reichel R, Nevins JR (1987) Role of an adenovirus E2 promoter binding factor in E1A-mediated coordinate gene control. Proc Natl Acad Sci USA 84:2180–2184

    Article  PubMed  CAS  Google Scholar 

  • Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930

    Article  PubMed  CAS  Google Scholar 

  • Kunkel TA (1985) Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci USA 82:488–492

    Article  PubMed  CAS  Google Scholar 

  • La Francois CJ, Jang YH, Cagin T, Goddard WA 3rd, Sowers LC (2000) Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water. Chem Res Toxicol 13:462–470

    Article  PubMed  CAS  Google Scholar 

  • Laird PW, Jaenisch R (1994) DNA methylation and cancer. Hum Mol Genet 3 Spec No:1487–1495

    Google Scholar 

  • Lao VV, Herring JL, Kim CH, Darwanto A, Soto U, Sowers LC (2009) Incorporation of 5-chlorocytosine into mammalian DNA results in heritable gene silencing and altered cytosine methylation patterns. Carcinogenesis 30:886–893

    Article  PubMed  CAS  Google Scholar 

  • Lee DH, Pfeifer GP (2003) Deamination of 5-methylcytosines within cyclobutane pyrimidine dimers is an important component of UVB mutagenesis. J Biol Chem 278:10314–10321

    Article  PubMed  CAS  Google Scholar 

  • Lefebvre A, Mauffret O, el Antri S, Monnot M, Lescot E, Fermandjian S (1995) Sequence dependent effects of CpG cytosine methylation. A joint 1H-NMR and 31P-NMR study. Eur J Biochem 229:445–454

    Article  PubMed  CAS  Google Scholar 

  • Lennartsson A, Ekwall K (2009) Histone modification patterns and epigenetic codes. Biochim Biophys Acta 1790:863–868

    PubMed  CAS  Google Scholar 

  • Lewis J, Bird A (1991) DNA methylation and chromatin structure. FEBS Lett 285:155–159

    Article  PubMed  CAS  Google Scholar 

  • Li L-C, Okino ST, Dahiya R (2004) DNA methylation in prostate cancer. Biochem Biophys Acta 1704:87–102

    PubMed  CAS  Google Scholar 

  • Lindahl T, Karlstrom O (1973) Heat-induced depyrimidination of deoxyribonucleic acid in neutral solution. Biochemistry 12:5151–5154

    Article  PubMed  CAS  Google Scholar 

  • Lindahl T, Nyberg B (1974) Heat-induced deamination of cytosine residues in deoxyribonucleic acid. Biochemistry 13:3405–3410

    Article  PubMed  CAS  Google Scholar 

  • List HJ, Patzel V, Zeidler U, Schopen A, Ruhl G, Stollwerk J, Klock G (1994) Methylation sensitivity of the enhancer from the human papillomavirus type 16. J Biol Chem 269:11902–11911

    PubMed  CAS  Google Scholar 

  • Liu P, Theruvathu JA, Darwanto A, Lao VV, Pascal T, Goddard W 3rd, Sowers LC (2008) Mechanisms of base selection by the Escherichia coli mispaired uracil glycosylase. J Biol Chem 283:8829–8836

    Article  PubMed  CAS  Google Scholar 

  • Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8Ă… resolution. Nature 389:251–260

    Article  PubMed  CAS  Google Scholar 

  • Makalowski W (2001) The human genome structure and organization. Acta Biochim Pol 48:587–598

    PubMed  CAS  Google Scholar 

  • Marcourt L, Cordier C, Couesnon T, Dodin G (1999) Impact of C5-cytosine methylation on the solution structure of d(GAAAACGTTTTC)2. An NMR and molecular modelling investigation. Eur J Biochem 265:1032–1042

    Article  PubMed  CAS  Google Scholar 

  • Mathers JC, McKay JA (2009) Epigenetic-potential contribution to fetal programming. Adv Exp Med Biol 646:119–123

    Article  PubMed  Google Scholar 

  • Mathison BH, Said B, Shank RC (1993) Effect of 5-methylcytosine as a neighboring base on methylation of DNA guanine by N-methyl-N-nitrosourea. Carcinogenesis 14:323–327

    Article  PubMed  CAS  Google Scholar 

  • Matter B, Wang G, Jones R, Tretyakova N (2004) Formation of diastereomeric benzo [a] pyrene diol epoxide-guanine adducts in p53 gene-derived DNA sequences. Chem Res Toxicol 17:731–741

    Article  PubMed  CAS  Google Scholar 

  • Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci USA 74:560–564

    Article  PubMed  CAS  Google Scholar 

  • Mayer-Jung C, Moras D, Timsit Y (1997) Effect of cytosine methylation on DNA-DNA recognition at CpG steps. J Mol Biol 270:328–335

    Article  PubMed  CAS  Google Scholar 

  • Mayer-Jung C, Moras D, Timsit Y (1998) Hydration and recognition of methylated CpG steps in DNA. EMBO J 17:2709–2718

    Article  PubMed  CAS  Google Scholar 

  • Mullaart E, Lohman PH, Berends F, Vijg J (1990) DNA damage metabolism and aging. Mutat Res 237:189–210

    PubMed  CAS  Google Scholar 

  • Nakase H, Takahama Y, Akamatsu Y (2003) Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage. EMBO Rep 4:774–780

    Article  PubMed  CAS  Google Scholar 

  • O’Gara M, Roberts RJ, Cheng X (1996) A structural basis for the preferential binding of hemimethylated DNA by HhaI DNA methyltransferase. J Mol Biol 263:597–606

    Article  PubMed  Google Scholar 

  • O’Neill RJ, Vorob’eva OV, Shahbakhti H, Zmuda E, Bhagwat AS, Baldwin GS (2003) Mismatch uracil glycosylase from Escherichia coli: a general mismatch or a specific DNA glycosylase? J Biol Chem 278:20526–20532

    Article  PubMed  CAS  Google Scholar 

  • Oda Y, Uesugi S, Ikehara M, Nishimura S, Kawase Y, Ishikawa H, Inoue H, Ohtsuka E (1991) NMR studies of a DNA containing 8-hydroxydeoxyguanosine. Nucleic Acids Res 19:1407–1412

    Article  PubMed  CAS  Google Scholar 

  • Ohmori H, Tomizawa JI, Maxam AM (1978) Detection of 5-methylcytosine in DNA sequences. Nucleic Acids Res 5:1479–2485

    Article  PubMed  CAS  Google Scholar 

  • Ooi SK, Bestor TH (2008) The colorful history of active DNA demethylation. Cell 133:1145–1148

    Article  PubMed  CAS  Google Scholar 

  • Patra SK, Patra A, Rizzi F, Ghosh TC, Bettuzzi S (2008) Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development. Cancer Metastasis Rev 27:315–334

    Article  PubMed  CAS  Google Scholar 

  • Paz MF, Fraga MF, Avila S, Guo M, Pollan M, Herman JG, Esteller M (2003) A systemic profile of DNA methylation in human cancer cell lines. Cancer Res 63:1114–1121

    PubMed  CAS  Google Scholar 

  • Pearl LH (2000) Structure and function in the uracil-DNA glycosylase superfamily. Mutat Res 460:165–181

    PubMed  CAS  Google Scholar 

  • Pffeifer GP, Denissenko MF (1998) Formation and repair of DNA lesions in the p53 gene: relation to cancer mutations? Environ Mol Mutagen 31:197–205

    Article  Google Scholar 

  • Pitt AR, Spickett CM (2008) Mass spectrometric analysis of HOCl- and free-radical-induced damage to lipids and proteins. Biochem Soc Trans 36:1077–1082

    Article  PubMed  CAS  Google Scholar 

  • Prendergast GC, Ziff EB (1991) Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science 251:186–189

    Article  PubMed  CAS  Google Scholar 

  • Prendergast GC, Lawe D, Ziff EB (1991) Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras contransformation. Cell 65:395–407

    Article  PubMed  CAS  Google Scholar 

  • Privat E, Sowers LC (1996) Photochemical deamination and demethylation of 5-methylcytosine. Chem Res Toxicol 9:745–750

    Article  PubMed  CAS  Google Scholar 

  • Pu WT, Struhl K (1992) Uracil interference, a rapid and general method for defining protein-DNA interactions involving the 5-methyl group of thymines: the GCN4-DNA complex. Nucleic Acids Res 20:771–775

    Article  PubMed  CAS  Google Scholar 

  • Radtke F, Hug M, Georgiev O, Matsuo K, Schaffner W (1996) Differential sensitivity of zinc finger transcription factors MTF-1, Sp1 and Krox-20 to CpG methylation of their binding sites. Biol Chem Hoppe Seyler 377:47–56

    PubMed  CAS  Google Scholar 

  • Ramsahoye BH, Davies CS, Mills KI (1996) DNA methylation: biology and significance. Blood Rev 10:249–261

    Article  PubMed  CAS  Google Scholar 

  • Razin A, Riggs AD (1980) DNA methylation and gene function. Science 210:604–610

    Article  PubMed  CAS  Google Scholar 

  • Rideout WM 3rd, Coetzee GA, Olumi AF, Jones PA (1990) 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science 249:1288–1290

    Article  PubMed  CAS  Google Scholar 

  • Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14:9–25

    Article  PubMed  CAS  Google Scholar 

  • Riggs AD, Jones PA (1983) 5-methylcytosine, gene regulation, and cancer. Adv Cancer Res 40:1–30

    Article  PubMed  CAS  Google Scholar 

  • Robertson KD, Jones PA (1997) Dynamic interrelationships between DNA replication, methylation, and repair. Am J Hum Genet 61:1220–1224

    Article  PubMed  CAS  Google Scholar 

  • Robertson KD, Jones PA (2000) DNA methylation: past, present and future directions. Carcinogenesis 21:461–467

    Article  PubMed  CAS  Google Scholar 

  • Rogstad DK, Liu P, Burdzy A, Lin SS, Sowers LC (2002) Endogenous DNA lesions can inhibit the binding of the AP-1 (c-Jun) transcription factor. Biochemistry 41:8093–8102

    Article  PubMed  CAS  Google Scholar 

  • Roll JD, Rivenbark AG, Jones WD, Coleman WB (2008) DNMT3b overexpression contributes to a hypermethylator phenotype in human breast cancer cell lines. Mol Cancer 7:15

    Article  PubMed  CAS  Google Scholar 

  • Rosen H, Crowley JR, Heinecke JW (2002) Human neutrophils use the myeloperoxidase-hydrogen peroxide-chloride system to chlorinate but not nitrate bacterial proteins during phagocytosis. J Biol Chem 277:30463–30468

    Article  PubMed  CAS  Google Scholar 

  • Rusmintratip V, Sowers LC (2000) An unexpectedly high excision capacity for mispaired 5-hydroxymethyluracil in human cell extracts. Proc Natl Acad Sci USA 97:14183–14187

    Article  PubMed  CAS  Google Scholar 

  • Scharer OD, Jiricny J (2001) Recent progress in the biology, chemistry and structural biology of DNA glycosylases. Bioessays 23:270–281

    Article  PubMed  CAS  Google Scholar 

  • Schiffer CA, Clifton IJ, Davisson VJ, Santi DV, Stroud RM (1995) Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry 34:16279–16287

    Article  PubMed  CAS  Google Scholar 

  • Schlagman SL, Hattman S (1989) The bacteriophage T2 and T4 DNA-[N6-adenine] methyltransferase (Dam) sequence specificities are not identical. Nucleic Acids Res 17:9101–9112

    Article  PubMed  CAS  Google Scholar 

  • Schorderet DF, Gartler SM (1992) Analysis of CpG suppression in methylated and nonmethylated species. Proc Natl Acad Sci USA 89:957–961

    Article  PubMed  CAS  Google Scholar 

  • Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31:27–36

    Article  PubMed  CAS  Google Scholar 

  • Shen ES, Whitlock JP Jr (1989) The potential role of DNA methylation in the response to 2,3,7,8-tetracholorodibenzo-p-dioxin. J Biol Chem 264:17754–17758

    PubMed  CAS  Google Scholar 

  • Shen JC, Rideout WM 3rd, Jones PA (1994) The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA. Nucleic Acids Res 22:972–976

    Article  PubMed  CAS  Google Scholar 

  • Smith SS, Kaplan BE, Sowers LC, Newman EM (1992) Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation. Proc Natl Acad Sci USA 89:4744–4748

    Article  PubMed  CAS  Google Scholar 

  • Son J, Pang B, McFaline JL, Taghizadeh K, Dedon PC (2008) Surveying the damage: the challenges of developing nucleic acid biomarkers of inflammation. Mol Biosyst 4:902–908

    Article  PubMed  CAS  Google Scholar 

  • Sowers LC, Beardsley GP (1993) Synthesis of oligonucleotides containing 5-(hydroxymethyl)-2’-deoxyuridine at defined sites. J Org Chem 58:1664–1665

    Article  CAS  Google Scholar 

  • Sowers LC, Shaw BR, Sedwick WD (1987) Base stacking and molecular polarizability: effect of a methyl group in the 5-position of pyrimidines. Biochem Biophys Res Commun 148:790–794

    Article  PubMed  CAS  Google Scholar 

  • Sowers LC, Sedwick WD, Shaw BR (1989) Hydrolysis of N3 –methyl-2’–deoxycytidine: model compound for reactivity of protonated cytosine residues in DNA. Mutat Res 215:131–138

    Article  PubMed  CAS  Google Scholar 

  • Steinberg JJ, Cajigas A, Brownlee M (1992) Enzymatic shot-gun 5’-phosphorylation and 3’-sister phosphate exchange: a two-dimensional thin-layer chromatographic technique to measure DNA deoxynucleotide modification. J Chromatogr 574:41–55

    Article  PubMed  CAS  Google Scholar 

  • Suquet C, Warren JJ, Seth N, Hurst JK (2010) Comparative study of HOCl-inflicted damage to bacterial DNA ex vivo and within cells. Arch Biochem Biophys 493:135–142

    Article  PubMed  CAS  Google Scholar 

  • Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935

    Article  PubMed  CAS  Google Scholar 

  • Tardy-Planechaud S, Fujimoto J, Lin SS, Sowers LC (1997) Solid phase synthesis and restriction endonuclease cleavage of oligodeoxynucleotides containing 5-(hydroxymethyl)-cytosine. Nucleic Acids Res 25:553–559

    Article  PubMed  CAS  Google Scholar 

  • The ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816

    Article  CAS  Google Scholar 

  • Thomas P, Fenech M (2008) Methylenetetrahydrofolate reductase, common polymorphisms, and relation to disease. Vitam Horm 79:375–392

    Article  PubMed  CAS  Google Scholar 

  • Timp W, Levchenko A, Feinberg AP (2009) A new link between epigenetic progenitor lesions in cancer and the dynamics of signal transduction. Cell Cycle 8:383–390

    Article  PubMed  CAS  Google Scholar 

  • Trinklein ND, Karaoz U, Wu J, Halees A, Force Aldred S, Collins PJ, Zheng D, Zhang ZD, Gerstein MB, Snyder M, Myers RM, Weng Z (2007) Integrated analysis of experimental data sets reveals many novel promoters in 1% of the human genome. Genome Res 17:720–731

    Article  PubMed  CAS  Google Scholar 

  • Turk PW, Laayoun A, Smith SS, Weitzman SA (1995) DNA adduct 8-hydroxyl-2’-deoxyguanosine (8-hydroxyguanine) affects function of human DNA methyltransferase. Carcinogenesis 16:1253–1255

    Article  PubMed  CAS  Google Scholar 

  • Valinluck V, Sowers LC (2007a) Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res 67:946–950

    Article  PubMed  CAS  Google Scholar 

  • Valinluck V, Sowers LC (2007b) Inflammation-mediated cytosine damage: a mechanistic link between inflammation and the epigenetic alterations in human cancers. Cancer Res 67:5583–5586

    Article  PubMed  CAS  Google Scholar 

  • Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC (2004) Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 32:4100–4108

    Article  PubMed  CAS  Google Scholar 

  • Valinluck V, Liu P, Kang JI Jr, Burdzy A, Sowers LC (2005) 5-halogenated pyrimidine lesions within a CpG sequence context mimic 5-methylcytosine by enhancing the binding of the methyl-CpG-binding domain of methyl-CpG-binding protein 2 (MeCP2). Nucleic Acids Res 33:3057–3064

    Google Scholar 

  • Valinluck V, Wu W, Liu P, Neidigh JW, Sowers LC (2006) Impact of cytosine 5-halogens on the interaction of DNA with restriction endonucleases and methyltransferase. Chem Res Toxicol 19:556–562

    Article  PubMed  CAS  Google Scholar 

  • van Wijnen AJ, van den Ent FM, Lian JB, Stein JL, Stein GS (1992) Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters. Mol Cell Biol 12:3273–3287

    PubMed  Google Scholar 

  • Vanyushin BF, Tkacheva SG, Belozersky AN (1970) Rare bases in animal DNA. Nature 225:948–949

    Article  PubMed  CAS  Google Scholar 

  • Vilpo JA, Vilpo LM (1991) Biochemical mechanisms by which reutilization of DNA 5-methylcytosine is prevented in human cells. Mutat Res 256:29–35

    PubMed  CAS  Google Scholar 

  • Vovis GF, Horiuchi K, Zinder ND (1974) Kinetics of methylation of DNA by a restriction endonuclease from Escherichia coli B. Proc Natl Acad Sci USA 71:3810–3813

    Article  PubMed  CAS  Google Scholar 

  • Wang RY, Gehrke CW, Ehrlich M (1980) Comparison of bisulfite modification of 5-methyldeoxycytidine and deoxycytidine residues. Nucleic Acids Res 8:4777–4790

    Article  PubMed  CAS  Google Scholar 

  • Wang RY, Kuo KC, Gehrke CW, Huang LH, Ehrlich M (1982) Heat- and alkali-induced deamination of 5-methylcytosine and cytosine residues in DNA. Biochim Biophys Acta 697:371–377

    PubMed  CAS  Google Scholar 

  • Watt F, Molloy PL (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 2:1136–1143

    Article  PubMed  CAS  Google Scholar 

  • Winterbourn CC, Kettle AJ (2000) Biomarkers of myeloperoxidase-derived hypochlorous acid. Free Radic Biol Med 29:403–409

    Article  PubMed  CAS  Google Scholar 

  • Wyatt GR, Cohen SS (1953) The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine. Biochem J 55:774–782

    PubMed  CAS  Google Scholar 

  • Yokomori N, Moore R, Negishi M (1995) Sexually dimorphic DNA demethylation in the promoter of the Slp (sex-limited protein) gene in mouse liver. Proc Natl Acad Sci USA 92:1302–1306

    Article  PubMed  CAS  Google Scholar 

  • Yoon JH, Smith LE, Feng Z, Tang MS, Lee CS, Pfeifer GP (2001) Methylated CpG dinucleotides are the preferential targets for G-to-T transversion mutations induced by benzo[a]pyrene diol epoxide in mammalian cells: similarities with the p53 mutation spectrum in smoking-associated lung cancers. Cancer Res 61:7110–7117

    PubMed  CAS  Google Scholar 

  • You YH, Pfeifer GP (2001) Similarities in sunlight-induced mutational spectra of CpG-methylated transgenes and the p53 gene in skin cancer point to an important role of 5-methylcytosine residues in solar UV mutagenesis. J Mol Biol 305:389–399

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Mathews CK (1994) Effect of DNA cytosine methylation upon deamination-induced mutagenesis in a natural target sequence in duplex DNA. J Biol Chem 269:7066–7069

    PubMed  CAS  Google Scholar 

  • Zhang H, Darwanto A, Linkhart TA, Sowers LC, Zhang L (2007) Maternal cocaine administration causes an epigenetic modification of protein kinase Cepsilon gene expression in fetal rat heart. Mol Pharmacol 71:1319–1328

    Article  PubMed  CAS  Google Scholar 

  • Zhu JK (2009) Active DNA demethylation mediated by DNA glycosylases. Annu Rev Genet 43:143–166

    Article  PubMed  CAS  Google Scholar 

  • Zingg JM, Jones PA (1997) Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis 18:869–882

    Article  PubMed  CAS  Google Scholar 

  • Zuo S, Boorstein RJ, Cunningham RP, Teebor GW (1995) Comparison of the effects of UV irradiation on 5-methyl-substituted and unsubstituted pyrimidines in alternating pyrimidine-purine sequences in DNA. Biochemistry 34:11582–11590

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA

    Lawrence C. Sowers

Authors
  1. Agus Darwanto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan D. Van Ornam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria Valinluck Lao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lawrence C. Sowers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence C. Sowers .

Editor information

Editors and Affiliations

  1. School of Medicine, Dept. Pharmacology, University of Pennsylvania, Hamilton Walk 3260, Philadelphia, 19104, Pennsylvania, USA

    Trevor M. Penning

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Darwanto, A., Van Ornam, J.D., Lao, V.V., Sowers, L.C. (2011). Chemical Carcinogenesis and Epigenetics. In: Penning, T. (eds) Chemical Carcinogenesis. Current Cancer Research. Humana Press. https://doi.org/10.1007/978-1-61737-995-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-61737-995-6_12

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61737-994-9

  • Online ISBN: 978-1-61737-995-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation