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PLOS ONE  2012 

Influence of Prenatal Arsenic Exposure and Newborn Sex on Global Methylation of Cord Blood DNA

DOI: 10.1371/journal.pone.0037147

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Abstract:

Background An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. Objective The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. Design Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs). Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. Results In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1) and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58) but negative among female newborns (N = 43); tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively) and for the association between maternal uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05). Conclusions These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm these findings and to examine the persistence of DNA methylation marks over time.

References

[1]  Kinniburgh DG, Smedley PL, Davies J, Milne C, Gaus I, et al. (2003) The scale and causes of the groundwater arsenic problem in Bangladesh. In: Welch A, Stollenwerk KG, editors. Arsenic in Ground Water: Geochemistry and Occurence: Kluwer Academic Publishers. pp. 211–257.
[2]  Smith AH, Lingas EO, Rahman M (2000) Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull World Health Organ 78: 1093–1103.
[3]  IARC W, editor. (2004) Some drinking-water disinfectants and contaminants, including arsenic: IARC Press.
[4]  Basu A, Mahata J, Gupta S, Giri AK (2001) Genetic toxicology of a paradoxical human carcinogen, arsenic: a review. Mutat Res 488: 171–194.
[5]  Vahter M (2000) Genetic polymorphism in the biotransformation of inorganic arsenic and its role in toxicity. Toxicol Lett 112–113: 209–217.
[6]  Waalkes MP, Ward JM, Liu J, Diwan BA (2003) Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice. Toxicol Appl Pharmacol 186: 7–17.
[7]  Waalkes MP, Liu J, Chen H, Xie Y, Achanzar WE, et al. (2004) Estrogen signaling in livers of male mice with hepatocellular carcinoma induced by exposure to arsenic in utero. J Natl Cancer Inst 96: 466–474.
[8]  Xie Y, Liu J, Benbrahim-Tallaa L, Ward JM, Logsdon D, et al. (2007) Aberrant DNA methylation and gene expression in livers of newborn mice transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic. Toxicology 236: 7–15.
[9]  Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, et al. (2006) Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood. Environ Health Perspect 114: 1293–1296.
[10]  Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Selvin S, et al. (2007) Acute myocardial infarction mortality in comparison with lung and bladder cancer mortality in arsenic-exposed region II of Chile from 1950 to 2000. Am J Epidemiol 166: 1381–1391.
[11]  Marshall G, Ferreccio C, Yuan Y, Bates MN, Steinmaus C, et al. (2007) Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst 99: 920–928.
[12]  Fry RC, Navasumrit P, Valiathan C, Svensson JP, Hogan BJ, et al. (2007) Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers. PLoS Genet 3: e207.
[13]  Ren X, McHale CM, Skibola CF, Smith AH, Smith MT, et al. (2011) An Emerging Role for Epigenetic Dysregulation in Arsenic Toxicity and Carcinogenesis. Environ Health Perspect 119: 11–19.
[14]  Reichard JF, Puga A (2010) Effects of arsenic exposure on DNA methylation and epigenetic gene regulation. Epigenomics 2: 87–104.
[15]  Chen H, Li S, Liu J, Diwan BA, Barrett JC, et al. (2004) Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis. Carcinogenesis 25: 1779–1786.
[16]  Okoji RS, Yu RC, Maronpot RR, Froines JR (2002) Sodium arsenite administration via drinking water increases genome-wide and Ha-ras DNA hypomethylation in methyl-deficient C57BL/6J mice. Carcinogenesis 23: 777–785.
[17]  Benbrahim-Tallaa L, Waterland RA, Styblo M, Achanzar WE, Webber MM, et al. (2005) 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 206: 288–298.
[18]  Reichard JF, Schnekenburger M, Puga A (2007) Long term low-dose arsenic exposure induces loss of DNA methylation. Biochem Biophys Res Commun 352: 188–192.
[19]  Sciandrello G, Caradonna F, Mauro M, Barbata G (2004) Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells. Carcinogenesis 25: 413–417.
[20]  Cui X, Wakai T, Shirai Y, Hatakeyama K, Hirano S (2006) Chronic oral exposure to inorganic arsenate interferes with methylation status of p16INK4a and RASSF1A and induces lung cancer in A/J mice. Toxicol Sci 91: 372–381.
[21]  Pilsner JR, Liu X, Ahsan H, Ilievski V, Slavkovich V, et al. (2007) Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults. Am J Clin Nutr 86: 1179–1186.
[22]  Pilsner JR, Liu X, Ahsan H, Ilievski V, Slavkovich V, et al. (2009) Folate deficiency, hyperhomocysteinemia, low urinary creatinine, and hypomethylation of leukocyte DNA are risk factors for arsenic-induced skin lesions. Environ Health Perspect 117: 254–260.
[23]  Majumdar S, Chanda S, Ganguli B, Mazumder DN, Lahiri S, et al. (2010) Arsenic exposure induces genomic hypermethylation. Environ Toxicol 25: 315–318.
[24]  Jo WJ, Ren X, Chu F, Aleshin M, Wintz H, et al. (2009) Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure. Toxicology and applied pharmacology 241: 294–302.
[25]  Zhou X, Li Q, Arita A, Sun H, Costa M (2009) Effects of nickel, chromate, and arsenite on histone 3 lysine methylation. Toxicology and applied pharmacology 236: 78–84.
[26]  Zhou X, Sun H, Ellen TP, Chen H, Costa M (2008) Arsenite alters global histone H3 methylation. Carcinogenesis 29: 1831–1836.
[27]  Hall M, Gamble M, Slavkovich V, Liu X, Levy D, et al. (2007) Determinants of arsenic metabolism: blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs. Environ Health Perspect 115: 1503–1509.
[28]  Cheng Z, Zheng Y, Mortlock R, van Geen A (2004) Rapid multi-element analysis of groundwater by high-resolution inductively coupled plasma mass spectrometry. Analytical and Bioanalytical Chemistry 379: 512–518.
[29]  Van Geen A, Cheng Z, Seddique AA, Hoque MA, Gelman A, et al. (2005) Reliability of a commercial kit to test groundwater for arsenic in Bangladesh. Environmental Science & Technology 39: 299–303.
[30]  Nixon DE, Mussmann GV, Eckdahl SJ, Moyer TP (1991) Total arsenic in urine: palladium-persulfate vs nickel as a matrix modifier for graphite furnace atomic absorption spectrophotometry. Clinical chemistry 37: 1575–1579.
[31]  Slot C (1965) Plasma creatinine determination. A new and specific Jaffe reaction method. Scandinavian journal of clinical and laboratory investigation 17: 381–387.
[32]  Balaghi M, Wagner C (1993) DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun 193: 1184–1190.
[33]  Pilsner JR, Hall MN, Liu X, Ahsan H, Ilievski V, et al. (2010) Associations of Plasma Selenium with Arsenic and Genomic Methylation of Leukocyte DNA in Bangladesh. Environ Health Perspect.
[34]  Choi IS, Estecio MR, Nagano Y, Kim do H, White JA, et al. (2007) Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol 20: 802–810.
[35]  Pilsner JR, Hu H, Ettinger A, Sanchez BN, Wright RO, et al. (2009) Influence of prenatal lead exposure on genomic methylation of cord blood DNA. Environ Health Perspect 117: 1466–1471.
[36]  Pilsner JR, Lazarus AL, Nam DH, Letcher RJ, Sonne C, et al. (2010) Mercury-associated DNA hypomethylation in polar bear brains via the LUminometric Methylation Assay: a sensitive method to study epigenetics in wildlife. Mol Ecol 19: 307–314.
[37]  Karimi M, Johansson S, Ekstrom TJ (2006) Using LUMA: a Luminometric-based assay for global DNA-methylation. Epigenetics 1: 45–48.
[38]  Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, et al. (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299: 2877–2883.
[39]  Gamble MV, Ahsan H, Liu X, Factor-Litvak P, Ilievski V, et al. (2005) Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. Am J Clin Nutr 81: 1372–1377.
[40]  Pfeiffer CM, Huff DL, Gunter EW (1999) Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin Chem 45: 290–292.
[41]  Gabory A, Attig L, Junien C (2009) Sexual dimorphism in environmental epigenetic programming. Mol Cell Endocrinol 304: 8–18.
[42]  Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, et al. (2009) DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Human molecular genetics 18: 4046–4053.
[43]  Yamagata Y, Asada H, Tamura I, Lee L, Maekawa R, et al. (2009) DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and estrogen. Human reproduction 24: 1126–1132.
[44]  Zhu ZZ, Hou L, Bollati V, Tarantini L, Marinelli B, et al. (2010) Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. International journal of epidemiology.
[45]  El-Maarri O, Becker T, Junen J, Manzoor SS, Diaz-Lacava A, et al. (2007) Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males. Human genetics 122: 505–514.
[46]  Nohara K, Baba T, Murai H, Kobayashi Y, Suzuki T, et al. (2011) Global DNA methylation in the mouse liver is affected by methyl deficiency and arsenic in a sex-dependent manner. Archives of toxicology 85: 653–661.
[47]  Ahsan H, Chen Y, Kibriya MG, Slavkovich V, Parvez F, et al. (2007) Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions in bangladesh. Cancer Epidemiol Biomarkers Prev 16: 1270–1278.
[48]  Gamble MV, Liu X, Ahsan H, Pilsner JR, Ilievski V, et al. (2006) Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. Am J Clin Nutr 84: 1093–1101.
[49]  Gamble MV, Liu X, Ahsan H, Pilsner R, Ilievski V, et al. (2005) Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect 113: 1683–1688.
[50]  Mudd SH, Poole JR (1975) Labile methyl balances for normal humans on various dietary regimens. Metabolism: clinical and experimental 24: 721–735.
[51]  Poole JR, Mudd SH, Conerly EB, Edwards WA (1975) Homocystinuria due to cystathionine synthase deficiency. Studies of nitrogen balance and sulfur excretion. The Journal of clinical investigation 55: 1033–1048.
[52]  Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiological reviews 80: 1107–1213.
[53]  Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, et al. (2005) Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environmental Health Perspectives 113: 192–200.
[54]  Gamble MV, Liu X (2005) Urinary creatinine and arsenic metabolism. Environmental Health Perspectives 113: A442; author reply A442–443.
[55]  Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R (2009) Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse. BMC developmental biology 9: 39.
[56]  Troisi R, Potischman N, Roberts JM, Harger G, Markovic N, et al. (2003) Correlation of serum hormone concentrations in maternal and umbilical cord samples. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 12: 452–456.
[57]  Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, et al. (2004) A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic acids research 32: e38.
[58]  Tost J, Gut IG (2007) DNA methylation analysis by pyrosequencing. Nat Protoc 2: 2265–2275.
[59]  Fazzari MJ, Greally JM (2004) Epigenomics: beyond CpG islands. Nature reviews Genetics 5: 446–455.
[60]  Rollins RA, Haghighi F, Edwards JR, Das R, Zhang MQ, et al. (2006) Large-scale structure of genomic methylation patterns. Genome Res 16: 157–163.
[61]  Tarantini L, Bonzini M, Apostoli P, Pegoraro P, Bollati V, et al. (2009) Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation. EHP 117: 217–222.
[62]  Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, et al. (2008) Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environmental health perspectives 116: 1547–1552.
[63]  Nelson HH, Marsit CJ, Kelsey KT (2011) Global methylation in exposure biology and translational medical science. Environmental Health Perspectives 119: 1528–1533.

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