Abstract
Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Chen Z, Wang JN, Ma GX, Zhang YS. China tackles the health effects of air pollution. Lancet 2013; 382(9909): 1959–1960
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674
Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer 2011; 11(10): 726–734
Sandoval J, Esteller M. Cancer epigenomics: beyond genomics. Curr Opin Genet Dev 2012; 22(1): 50–55
You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 2012; 22(1): 9–20
Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012; 150(1): 12–27
Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004; 4(2): 143–153
Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009; 23(7): 781–783
Inst Health Metrics & Evaluation, Global Burden of Disease Cause Patterns 2010, available at: go.nature.com/brc4nw
Deweerdt S. Aetiology: crucial clues. Nature 2014; 513(7517): S12–S13
Loomis D, Grosse Y, Lauby-Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Baan R, Mattock H, Straif K. International Agency for Research on Cancer MonographWorking Group IARC: the carcinogenicity of outdoor air pollution. Lancet Oncol 2013; 14(13): 1262–1263
Watson T. Environment: breathing trouble. Nature 2014; 513 (7517): S14–S15
Yang G, Wang Y, Zeng Y, Gao GF, Liang X, Zhou M, Wan X, Yu S, Jiang Y, Naghavi M, Vos T, Wang H, Lopez AD, Murray CJ. Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 2013; 381(9882): 1987–2015
Raaschou-Nielsen O, Andersen ZJ, Beelen R, Samoli E, Stafoggia M, Weinmayr G, Hoffmann B, Fischer P, Nieuwenhuijsen MJ, Brunekreef B, Xun WW, Katsouyanni K, Dimakopoulou K, Sommar J, Forsberg B, Modig L, Oudin A, Oftedal B, Schwarze PE, Nafstad P, De Faire U, Pedersen NL, Ostenson CG, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Sørensen M, Tjnneland A, Ellermann T, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita B, Key TJ, de Hoogh K, Concin H, Nagel G, Vilier A, Grioni S, Krogh V, Tsai MY, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Tamayo I, Amiano P, Dorronsoro M, Trichopoulou A, Bamia C, Vineis P, Hoek G. Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Lancet Oncol 2013; 14(9): 813–822
Subbaraman N. Public health:a burning issue. Nature 2014; 513: S16–S17
Cao Y, Gao H. Prevalence and causes of air pollution and lung cancer in Xuanwei City and Fuyuan County, Yunnan Province, China. Front Med 2012; 6(2): 217–220
Xiao Y, Shao Y, Yu X, Zhou G. The epidemic status and risk factors of lung cancer in Xuanwei City, Yunnan Province, China. Front Med 2012; 6(4): 388–394
Mumford JL, He XZ, Chapman RS, Cao SR, Harris DB, Li XM, Xian YL, Jiang WZ, Xu CW, Chuang JC, Wilson WE, Cooke M. Lung cancer and indoor air pollution in Xuan Wei, China. Science 1987; 235(4785): 217–220
Oey H, Whitelaw E. On the meaning of the word “epimutation”. Trends Genet 2014; 30(12): 519–520
Sincic N, Herceg Z. DNA methylation and cancer: ghosts and angels above the genes. Curr Opin Oncol 2011; 23(1): 69–76
Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 2009; 113(25): 6411–6418
Hovestadt V, Jones DT, Picelli S, Wang W, Kool M, Northcott PA, Sultan M, Stachurski K, Ryzhova M, Warnatz HJ, Ralser M, Brun S, Bunt J, Jäger N, Kleinheinz K, Erkek S, Weber UD, Bartholomae CC,von Kalle C, Lawerenz C, Eils J, Koster J, Versteeg R, Milde T, Witt O, Schmidt S, Wolf S, Pietsch T, Rutkowski S, Scheurlen W, Taylor MD, Brors B, Felsberg J, Reifenberger G, Borkhardt A, Lehrach H, Wechsler-Reya RJ, Eils R, Yaspo ML, Landgraf P, Korshunov A, Zapatka M, Radlwimmer B, Pfister SM, Lichter P. Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature 2014; 510(7506): 537–541
James SR, Cedeno CD, Sharma A, Zhang W, Mohler JL, Odunsi K, Wilson EM, Karpf AR. DNA methylation and nucleosome occupancy regulate the cancer germline antigen gene MAGEA11. Epigenetics 2013; 8(8): 849–863
Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci USA 2000; 97(10): 5237–5242
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009; 462(7271): 315–322
Baer C, Claus R, Plass C. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 2013; 73(2): 473–477
Lopez-Serra P, Esteller M. DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene 2012; 31 (13): 1609–1622
Bell AC, Felsenfeld G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 2000; 405(6785): 482–485
Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell 2005; 8(2): 89–91
Kulis M, Heath S, Bibikova M, Queirós AC, Navarro A, Clot G, Martínez-Trillos A, Castellano G, Brun-Heath I, Pinyol M, Barberán-Soler S, Papasaikas P, Jares P, Beà S, Rico D, Ecker S, Rubio M, Royo R, Ho V, Klotzle B, Hernández L, Conde L, López-Guerra M, Colomer D, Villamor N, Aymerich M, Rozman M, Bayes M, Gut M, Gelpí JL, Orozco M, Fan JB, Quesada V, Puente XS, Pisano DG, Valencia A, López-Guillermo A, Gut I, López-Otín C, Campo E, Martín-Subero JI. Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nat Genet 2012; 44(11): 1236–1242
Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, D’Souza C, Fouse SD, Johnson BE, Hong C, Nielsen C, Zhao Y, Turecki G, Delaney A, Varhol R, Thiessen N, Shchors K, Heine VM, Rowitch DH, Xing X, Fiore C, Schillebeeckx M, Jones SJ, Haussler D, Marra MA, Hirst M, Wang T, Costello JF. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 2010; 466(7303): 253–257
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009; 462(7271): 315–322
Yang X, Han H, De Carvalho DD, Lay FD, Jones PA, Liang G. Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell 2014; 26(4): 577–590
Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP. Genome-wide methylation analysis of human colon cancer reveals similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009; 41: 178–186
Kanai Y, Ushijima S, Nakanishi Y, Sakamoto M, Hirohashi S. Mutation of the DNA methyltransferase (DNMT) 1 gene in human colorectal cancers. Cancer Lett 2003; 192(1): 75–82
Yan XJ, Xu J, Gu ZH, Pan CM, Lu G, Shen Y, Shi JY, Zhu YM, Tang L, Zhang XW, Liang WX, Mi JQ, Song HD, Li KQ, Chen Z, Chen SJ. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011; 43(4): 309–315
Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE, Absher DM, Wold BJ,Myers RM. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res 2013; 23(3): 555–567
Schuster-Böckler B, Lehner B. Chromatin organization is a major influence on regional mutation rates in human cancer cells. Nature 2012; 488(7412): 504–507
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Lee RS, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CW, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013; 499(7457): 214–218
Polak P, Karlic R, Koren A, Thurman R, Sandstrom R, Lawrence MS, Reynolds A, Rynes E, Vlahovicek K, Stamatoyannopoulos JA, Sunyaev SR. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 2015; 518(7539): 360–364
Hitchins MP, Rapkins RW, Kwok CT, Srivastava S, Wong JJ, Khachigian LM, Polly P, Goldblatt J, Ward RL. Dominantly inherited constitutional epigenetic silencing of MLH1 in a canceraffected family is linked to a single nucleotide variant within the 5' UTR. Cancer Cell 2011; 20(2): 200–213
Guerrero-Presto R, Michailidi C, Marchionni L, Pickering CR, Frederick MJ, Myers JN, Yegnasubramanian S, Hadar T, Noordhuis MG, Zizkova V, Fertig E, Agrawal N, Westra W, Koch W, Califano J, Velculescu VE, Sidransky D. Key tumor suppressor genes inactivated by “greater promoter” methylation and somatic mutations in head and neck cancer. Epigenetics 2014; 9: 1031–1046
Tomasetti C, Vogelstein B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2015; 347(6217): 78–81
Roadmap Epigenomics Consortium; Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA,Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature 2015; 518(7539): 317–330
Wu J, Wang SH, Potter D, Liu JC, Smith LT, Wu YZ, Huang TH, Plass C. Diverse histone modifications on histone 3 lysine 9 and their relation to DNA methylation in specifying gene silencing. BMC Genomics 2007; 8(1): 131
Bannister AJ, Kouzarides T. Reversing histone methylation. Nature 2005; 436(7054): 1103–1106
Teneng I, Montoya-Durango DE, Quertermous JL, Lacy ME, Ramos KS. Reactivation of L1 retrotransposon by benzo(a)pyrene involves complex genetic and epigenetic regulation. Epigenetics 2011; 6(3): 355–367
Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 2006; 31(2): 89–97
Bhutani N, Burns DM, Blau HM. DNA demethylation dynamics. Cell 2011; 146(6): 866–872
Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil Steril 2007; 87(1): 24–32
Tan AY, Manley JL. The TET family of proteins: functions and roles in disease. J Mol Cell Biol 2009; 1(2): 82–92
Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AW, Lu C, Ward PS, Thompson CB, Kaufman A, Guryanova O, Levine R, Heguy A, Viale A, Morris LG, Huse JT, Mellinghoff IK, Chan TA. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012; 483 (7390): 479–483
Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr 2009; 21(2): 243–251
Yang P, Ma J, Zhang B, Duan H, He Z, Zeng J, Zeng X, Li D, Wang Q, Xiao Y, Liu C, Xiao Q, Chen L, Zhu X, Xing X, Li Z, Zhang S, Zhang Z, Ma L, Wang E, Zhuang Z, Zheng Y, Chen W. CpG site-specific hypermethylation of p16INK4a in peripheral blood lymphocytes of PAH-exposed workers. Cancer Epidemiol Biomarkers Prev 2012; 21(1): 182–190
Herbstman JB, Tang D, Zhu D, Qu L, Sjödin A, Li Z, Camann D, Perera FP. Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood. Environ Health Perspect 2012; 120(5): 733–738
Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM. Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS ONE 2009; 4(2): e4488
Tang WY, Levin L, Talaska G, Cheung YY, Herbstman J, Tang D, Miller RL, Perera F, Ho SM. Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-λ in cord white blood cells. Environ Health Perspect 2012; 120(8): 1195–1200
Shenker NS, Ueland PM, Polidoro S, van Veldhoven K, Ricceri F, Brown R, Flanagan JM, Vineis P. DNA methylation as a long-term biomarker of exposure to tobacco smoke. Epidemiology 2013; 24 (5): 712–716
Corrales J, Fang X, Thornton C, Mei W, Barbazuk WB, Duke M, Scheffler BE, Willett KL. Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a] pyrene exposure. Comp Biochem Physiol C Toxicol Pharmacol 2014; 163: 37–46
Huang H, Hu G, Cai J, Xia B, Liu J, Li X, Gao W, Zhang J, Liu Y, Zhuang Z. Role of poly(ADP-ribose) glycohydrolase silencing in DNA hypomethylation induced by benzo(a)pyrene. Biochem Biophys Res Commun 2014; 452(3): 708–714
Zeng JL, Zhang B, Yang P, Xiao YM, Wei Q, Wang Q, Li DC, Xing XM, Chen LP, Chen W. A genome-wide screen for promoterspecific sites of differential DNA methylation during human cell malignant transformation in vitro. Chin J Prev Med (Zhonghua Yu Fang Yi Xue Za Zhi) 2011; 45(5): 404–409 (in Ch_e)
Damiani LA, Yingling CM, Leng S, Romo PE, Nakamura J, Belinsky SA. Carcinogen-induced gene promoter hypermethylation is mediated by DNMT1 and causal for transformation of immortalized bronchial epithelial cells. Cancer Res 2008; 68(21): 9005–9014
Sadikovic B, Andrews J, Rodenhiser DI. DNA methylation analysis using CpG microarrays is impaired in benzopyrene exposed cells. Toxicol Appl Pharmacol 2007; 225(3): 300–309
Liu F, Killian JK, Yang M, Walker RL, Hong JA, Zhang M, Davis S, Zhang Y, Hussain M, Xi S, Rao M, Meltzer PA, Schrump DS. Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 2010; 29(25): 3650–3664
Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B, Cantone L, Rizzo G, Hou L, Schwartz J, Bertazzi PA, Baccarelli A. Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect 2009; 117(2): 217–222
Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 2009; 179(7): 572–578
Herceg Z, Vaissière T. Epigenetic mechanisms and cancer: an interface between the environment and the genome. Epigenetics 2011; 6(7): 804–819
Belinsky SA, Snow SS, Nikula KJ, Finch GL, Tellez CS, Palmisano WA. Aberrant CpG island methylation of the p16 (INK4a) and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. Carcinogenesis 2002; 23(2): 335–339
Hou L, Zhang X, Zheng Y, Wang S, Dou C, Guo L, Byun HM, Motta V, McCracken J, Díaz A, Kang CM, Koutrakis P, Bertazzi PA, Li J, Schwartz J, Baccarelli AA. Altered methylation in tandem repeat element and elemental component levels in inhalable air particles. Environ Mol Mutagen 2014; 55(3): 256–265
Carmona JJ, Sofer T, Hutchinson J, Cantone L, Coull B, Maity A, Vokonas P, Lin X, Schwartz J, Baccarelli AA. Short-term airborne particulate matter exposure alters the epigenetic landscape of human genes associated with the mitogen-activated protein kinase network: a cross-sectional study. Environ Health 2014; 13(1): 94
Lepeule J, Bind MA, Baccarelli AA, Koutrakis P, Tarantini L, Litonjua A, Sparrow D, Vokonas P, Schwartz JD. Epigenetic influences on associations between air pollutants and lung function in elderly men: the normative aging study. Environ Health Perspect 2014; 122(6): 566–572
Bind MA, Lepeule J, Zanobetti A, Gasparrini A, Baccarelli A, Coull BA, Tarantini L, Vokonas PS, Koutrakis P, Schwartz J. Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis. Epigenetics 2014; 9(3): 448–458
De Prins S, Koppen G, Jacobs G, Dons E, Van de Mieroop E, Nelen V, Fierens F, Int Panis L, De Boever P, Cox B, Nawrot TS, Schoeters G. Influence of ambient air pollution on global DNA methylation in healthy adults: a seasonal follow-up. Environ Int 2013; 59: 418–424
Sofer T, Baccarelli A, Cantone L, Coull B, Maity A, Lin X, Schwartz J. Exposure to airborne particulate matter is associated with methylation pattern in the asthma pathway. Epigenomics 2013; 5(2): 147–154
Bind MA, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P, Schwartz J. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigeneenvironment interactions in an elderly cohort. Epidemiology 2012; 23(2): 332–340
Madrigano J, Baccarelli A, Mittleman MA, Wright RO, Sparrow D, Vokonas PS, Tarantini L, Schwartz J. Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men. Environ Health Perspect 2011; 119(7): 977–982
Chanda S, Dasgupta UB, Guhamazumder D, Gupta M, Chaudhuri U, Lahiri S, Das S, Ghosh N, Chatterjee D. DNA methylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancy. Toxicol Sci 2006; 89(2): 431–437
Benbrahim-Tallaa L, Waterland RA, Styblo M, Achanzar WE, Webber MM, Waalkes MP. Molecular events associated with arsenic-induced malignant transformation of human prostatic epithelial cells: aberrant genomic DNA methylation and K-ras oncogene activation. Toxicol Appl Pharmacol 2005; 206(3): 288–298
Jensen TJ, Novak P, Wnek SM, Gandolfi AJ, Futscher BW. Arsenicals produce stable progressive changes in DNA methylation patterns that are linked to malignant transformation of immortalized urothelial cells. Toxicol Appl Pharmacol 2009; 241 (2): 221–229
Tabish AM, Poels K, Hoet P, Godderis L. Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells. PLoS ONE 2012; 7(4): e34674
Liu Q, Yang L, Gong C, Tao G, Huang H, Liu J, Zhang H, Wu D, Xia B, Hu G, Wang K, Zhuang Z. Effects of long-term low-dose formaldehyde exposure on global genomic hypomethylation in 16HBE cells. Toxicol Lett 2011; 205(3): 235–240
Bastide K, Guilly MN, Bernaudin JF, Joubert C, Lectard B, Levalois C, Malfoy B, Chevillard S. Molecular analysis of the Ink4a/Rb1-Arf/Tp53 pathways in radon-induced rat lung tumors. Lung Cancer 2009; 63(3): 348–353
Su S, Jin Y, Zhang W, Yang L, Shen Y, Cao Y, Tong J. Aberrant promoter methylation of p16(INK4a) and O(6)-methylguanine- DNA methyltransferase genes in workers at a Chinese uranium mine. J Occup Health 2006; 48(4): 261–266
Scott BR, Belinsky SA, Leng S, Lin Y, Wilder JA, Damiani LA. Radiation-stimulated epigenetic reprogramming of adaptiveresponse genes in the lung: an evolutionary gift for mounting adaptive protection against lung cancer. Dose Response 2009; 7(2): 104–131
Andujar P, Wang J, Descatha A, Galateau-Sallé F, Abd-Alsamad I, Billon-Galland MA, Blons H, Clin B, Danel C, Housset B, Laurent-Puig P, Le Pimpec-Barthes F, Letourneux M, Monnet I, Régnard JF, Renier A, Zucman-Rossi J, Pairon JC, Jaurand MC. p16INK4A inactivation mechanisms in non-small-cell lung cancer patients occupationally exposed to asbestos. Lung Cancer 2010; 67 (1): 23–30
Christensen BC, Houseman EA, Godleski JJ, Marsit CJ, Longacker JL, Roelofs CR, Karagas MR, Wrensch MR, Yeh RF, Nelson HH, Wiemels JL, Zheng S, Wiencke JK, Bueno R, Sugarbaker DJ, Kelsey KT. Epigenetic profiles distinguish pleural mesothelioma from normal pleura and predict lung asbestos burden and clinical outcome. Cancer Res 2009; 69(1): 227–234
Christensen BC, Godleski JJ, Marsit CJ, Houseman EA, Lopez-Fagundo CY, Longacker JL, Bueno R, Sugarbaker DJ, Nelson HH, Kelsey KT. Asbestos exposure predicts cell cycle control gene promoter methylation in pleural mesothelioma. Carcinogenesis 2008; 29(8): 1555–1559
Sha Y, Zhou W, Yang Z, Zhu X, Xiang Y, Li T, Zhu D, Yang X. Changes in poly(ADP-ribosyl)ation patterns in workers exposed to BTX. PLoS ONE 2014; 9(9): e106146
Yang J, Bai W, Niu P, Tian L, Gao A. Aberrant hypomethylated STAT3 was identified as a biomarker of chronic benzene poisoning through integrating DNA methylation and mRNA expression data. Exp Mol Pathol 2014; 96(3): 346–353
Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D, Byun HM, Jiang J, Marinelli B, Pesatori AC, Bertazzi PA, Yang AS. Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res 2007; 67(3): 876–880
Chappell G, Kobets T, O’Brien B, Tretyakova N, Sangaraju D, Kosyk O, Sexton KG, Bodnar W, Pogribny IP, Rusyn I. Epigenetic events determine tissue-specific toxicity of inhalational exposure to the genotoxic chemical 1,3-butadiene in male C57BL/6J mice. Toxicol Sci 2014; 142(2): 375–384
Koturbash I, Scherhag A, Sorrentino J, Sexton K, Bodnar W, Swenberg JA, Beland FA, Pardo-Manuel Devillena F, Rusyn I, Pogribny IP. Epigenetic mechanisms of mouse interstrain variability in genotoxicity of the environmental toxicant 1,3- butadiene. Toxicol Sci 2011; 122(2): 448–456
Koturbash I, Scherhag A, Sorrentino J, Sexton K, Bodnar W, Tryndyak V, Latendresse JR, Swenberg JA, Beland FA, Pogribny IP, Rusyn I. Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene. Environ Health Perspect 2011; 119(5): 635–640
Zhuang SM, Schippert A, Haugen-Strano A, Wiseman RW, Söderkvist P. Inactivations of p16INK4a-a, p16INK4a-ß and p15INK4b genes in 2',3'-dideoxycytidine- and 1,3-butadieneinduced murine lymphomas. Oncogene 1998; 16(6): 803–808
Mathison BH, Frame SR, Bogdanffy MS. DNA methylation, cell proliferation, and histopathology in rats following repeated inhalation exposure to dimethyl sulfate. Inhal Toxicol 2004; 16 (9): 581–592
Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, Bonefeld-Jorgensen EC. Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environ Health Perspect 2008; 116(11): 1547–1552
Kostka G, Urbanek-Olejnik K, Liszewska M, Winczura A. The effect of acute dichlorodiphenyltrichloroethane exposure on hypermethylation status and down-regulation of p53 and p16 (INK4a) genes in rat liver. Environ Toxicol 2014 Nov 20. [Epub ahead of print] doi: 10.1002/tox.22071
Shutoh Y, Takeda M, Ohtsuka R, Haishima A, Yamaguchi S, Fujie H, Komatsu Y, Maita K, Harada T. Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats: implication of hormesis-like effects. J Toxicol Sci 2009; 34(5): 469–482
Li C, Yang X, Xu M, Zhang J, Sun N. Epigenetic marker (LINE-1 promoter) methylation level was associated with occupational lead exposure. Clin Toxicol (Phila) 2013; 51(4): 225–229
Li YY, Chen T, Wan Y, Xu SQ. Lead exposure in pheochromocytoma cells induces persistent changes in amyloid precursor protein gene methylation patterns. Environ Toxicol 2012; 27(8): 495–502
Hanna CW, Bloom MS, Robinson WP, Kim D, Parsons PJ, vom Saal FS, Taylor JA, Steuerwald AJ, Fujimoto VY. DNA methylation changes in whole blood is associated with exposure to the environmental contaminants, mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF. Hum Reprod 2012; 27(5): 1401–1410
Li C, Xu M, Wang S, Yang X, Zhou S, Zhang J, Liu Q, Sun Y. Lead exposure suppressed ALAD transcription by increasing methylation level of the promoter CpG islands. Toxicol Lett 2011; 203(1): 48–53
Lou J, Wang Y, Yao C, Jin L, Wang X, Xiao Y, Wu N, Song P, Song Y, Tan Y, Gao M, Liu K, Zhang X. Role of DNA methylation in cell cycle arrest induced by Cr (VI) in two cell lines. PLoS ONE 2013; 8(8): e71031
Wang TC, Song YS, Wang H, Zhang J, Yu SF, Gu YE, Chen T, Wang Y, Shen HQ, Jia G. Oxidative DNA damage and global DNA hypomethylation are related to folate deficiency in chromate manufacturing workers. J Hazard Mater 2012; 213–214: 440–446
Proctor DM, Suh M, Campleman SL, Thompson CM. Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures. Toxicology 2014; 325: 160–179
Ali AH, Kondo K, Namura T, Senba Y, Takizawa H, Nakagawa Y, Toba H, Kenzaki K, Sakiyama S, Tangoku A. Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure. Mol Carcinog 2011; 50(2): 89–99
Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 2014; 122(9): 946–954
Weng S, Wang W, Li Y, Li H, Lu X, Xiao S, Wu T, Xie M, Zhang W. Continuous cadmium exposure from weaning to maturity induces downregulation of ovarian follicle development-related SCF/c-kit gene expression and the corresponding changes of DNA methylation/microRNA pattern. Toxicol Lett 2014; 225(3): 367–377
Pierron F, Baillon L, Sow M, Gotreau S, Gonzalez P. Effect of lowdose cadmium exposure on DNA methylation in the endangered European eel. Environ Sci Technol 2014; 48(1): 797–803
Sanders AP, Smeester L, Rojas D, DeBussycher T, Wu MC, Wright FA, Zhou YH, Laine JE, Rager JE, Swamy GK, Ashley-Koch A, Lynn Miranda M, Fry RC. Cadmium exposure and the epigenome: Exposure-associated patterns of DNA methylation in leukocytes from mother-baby pairs. Epigenetics 2014; 9(2): 212–221
Yuan D, Ye S, Pan Y, Bao Y, Chen H, Shao C. Long-term cadmium exposure leads to the enhancement of lymphocyte proliferation via down-regulating p16 by DNA hypermethylation. Mutat Res 2013; 757(2): 125–131
Turdi S, Sun W, Tan Y, Yang X, Cai L, Ren J. Inhibition of DNA methylation attenuates low-dose cadmium-induced cardiac contractile and intracellular Ca(2+) anomalies. Clin Exp Pharmacol Physiol 2013; 40(10): 706–712
Zhang C, Liang Y, Lei L, Zhu G, Chen X, Jin T, Wu Q. Hypermethylations of RASAL1 and KLOTHO is associated with renal dysfunction in a Chinese population environmentally exposed to cadmium. Toxicol Appl Pharmacol 2013; 271(1): 78–85
Kippler M, Engström K, Mlakar SJ, Bottai M, Ahmed S, Hossain MB, Raqib R, Vahter M, Broberg K. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight. Epigenetics 2013; 8(5): 494–503
Yanez Barrientos E, Wrobel K, Lopez Torres A, Gutiérrez Corona F, Wrobel K. Application of reversed-phase high-performance liquid chromatography with fluorimetric detection for simultaneous assessment of global DNA and total RNA methylation in Lepidium sativum: effect of plant exposure to Cd(II) and Se(IV). Anal Bioanal Chem 2013; 405(7): 2397–2404
Huang D, Zhang Y, Qi Y, Chen C, Ji W. Global DNA hypomethylation, rather than reactive oxygen species (ROS), a potential facilitator of cadmium-stimulated K562 cell proliferation. Toxicol Lett 2008; 179(1): 43–47
Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP. Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res 2003; 286(2): 355–365
Benbrahim-Tallaa L, Waterland RA, Dill AL, Webber MM, Waalkes MP. Tumor suppressor gene inactivation during cadmium- induced malignant transformation of human prostate cells correlates with overexpression of de novo DNA methyltransferase. Environ Health Perspect 2007; 115(10): 1454–1459
Zhou ZH, Lei YX, Wang CX. Analysis of aberrant methylation in DNA repair genes during malignant transformation of human bronchial epithelial cells induced by cadmium. Toxicol Sci 2012; 125(2): 412–417
Ji W, Yang L, Yu L, Yuan J, Hu D, Zhang W, Yang J, Pang Y, Li W, Lu J, Fu J, Chen J, Lin Z, Chen W, Zhuang Z. Epigenetic silencing of O6-methylguanine DNA methyltransferase gene in NiS-transformed cells. Carcinogenesis 2008; 29(6): 1267–1275
Yang J, Chen W, Li X, Sun J, Guo Q, Wang Z. Relationship between urinary nickel and methylation of p15, p16 in workers exposed to nickel. J Occup Environ Med 2014; 56(5): 489–492
Zhang J, Zhou Y, Wu YJ, Li MJ, Wang RJ, Huang SQ, Gao RR, Ma L, Shi HJ, Zhang J. Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis. Toxicol Lett 2013; 223(1): 42–51
Tajuddin SM, Amaral AF, Fernández AF, Rodríguez-Rodero S, Rodríguez RM, Moore LE, Tardón A, Carrato A, García-Closas M, Silverman DT, Jackson BP, García-Closas R, Cook AL, Cantor KP, Chanock S, Kogevinas M, Rothman N, Real FX, Fraga MF, Malats N; Spanish Bladder Cancer/EPICURO Study Investigators. Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA. Environ Health Perspect 2013; 121(6): 650–656
Wu CH, Tang SC, Wang PH, Lee H, Ko JL. Nickel-induced epithelial-mesenchymal transition by reactive oxygen species generation and E-cadherin promoter hypermethylation. J Biol Chem 2012; 287(30): 25292–25302
Zhang J, Zhang J, Li M,Wu Y, Fan Y, Zhou Y, Tan L, Shao Z, Shi H. Methylation of RAR-ß2, RASSF1A, and CDKN2A genes induced by nickel subsulfide and nickel-carcinogenesis in rats. Biomed Environ Sci 2011; 24(2): 163–171
Coulter JB, O’Driscoll CM, Bressler JP. Hydroquinone increases 5-hydroxymethylcytosine formation through ten eleven translocation 1 (TET1) 5-methylcytosine dioxygenase. J Biol Chem 2013; 288(40): 28792–28800
Zhang Y, Yang R, Burwinkel B, Breitling LP, Brenner H. F2RL3 methylation as a biomarker of current and lifetime smoking exposures. Environ Health Perspect 2014; 122(2): 131–137
Lima SC, Hernandez-Vargas H, Herceg Z. Epigenetic signatures in cancer: Implications for the control of cancer in the clinic. Curr Opin Mol Ther 2010; 12(3): 316–324
Singh V, Sharma P, Capalash N. DNA methyltransferase-1 inhibitors as epigenetic therapy for cancer. Curr Cancer Drug Targets 2013; 13(4): 379–399
Vizoso M, Esteller M. German-Catalan workshop on epigenetics and cancer. Epigenetics 2013; 8(9): 998–1003
Vaissière T, Hung RJ, Zaridze D, Moukeria A, Cuenin C, Fasolo V, Ferro G, Paliwal A, Hainaut P, Brennan P, Tost J, Boffetta P, Herceg Z. Quantitative analysis of DNA methylation profiles in lung cancer identifies aberrant DNA methylation of specific genes and its association with gender and cancer risk factors. Cancer Res 2009; 69(1): 243–252
Belinsky SA, Grimes MJ, Casas E, Stidley CA, Franklin WA, Bocklage TJ, Johnson DH, Schiller JH. Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum. Br J Cancer 2007; 96(8): 1278–1283
Shenker NS, Polidoro S, van Veldhoven K, Sacerdote C, Ricceri F, Birrell MA, Belvisi MG, Brown R, Vineis P, Flanagan JM. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet 2013; 22(5): 843–851
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cao, Y. Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications. Front. Med. 9, 261–274 (2015). https://doi.org/10.1007/s11684-015-0406-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11684-015-0406-y