Abstract
Purpose
To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state.
Methods
A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function.
Results
Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2 = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure.
Conclusions
Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.
Similar content being viewed by others
References
Abe T, Oda J, Takizawa Y, Suzuki E, Gejyo F (2008) Evaluation of serum fibrosis markers in asbestos-exposed workers. Nihon Kokyuki Gakkai Zasshi 46:875–879
Abejie BA, Wang X, Kales SN, Christiani DC (2010) Patterns of pulmonary dysfunction in asbestos workers: a cross-sectional study. J Occup Med Toxicol 5:12
Adib G, Labreche F, De Guire L, Dion C, Dufresne A (2013) Short, fine and WHO asbestos fibers in the lungs of quebec workers with an asbestos-related disease. Am J Ind Med 56:1001–1014
Alfonso H, Franklin P, Ching S, Croft K, Burcham P, Olsen N, Reid A, Joyce D, de Klerk N, Musk AB (2015) Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: A double-blind, randomized clinical trial. Respirology 20:1102–1107
Ameille J, Letourneux M, Paris C, Brochard P, Stoufflet A, Schorle E, Gislard A, Laurent F, Conso F, Pairon J (2010) Does asbestos exposure cause airway obstruction, in the absence of confirmed asbestosis? Am J Respir Crit Care Med 182:526–530
American Thoracic Society (2004) Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med 170:691–715
Biancotto A, Wank A, Perl S, Cook W, Olnes MJ, Dagur PK, Fuchs JC, Langweiler M, Wang E, McCoy JP (2015) Correction: baseline levels and temporal stability of 27 multiplexed serum cytokine concentrations in healthy subjects. PLoS One 10:e132870
Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D, Byun HM, Jiang J, Marinelli B, Pesatori AC, Bertazzi PA, Yang AS (2007) Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res 67:876–880
Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A (2000) Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci 923:68–77
Brown TA, Lee JW, Holian A, Porter V, Fredriksen H, Kim M, Cho YH (2016) Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure. Nanotoxicology 10:453–461
Chien JW, Au DH, Barnett MJ, Goodman GE (2007) Spirometry, rapid FEV1 decline, and lung cancer among asbestos exposed heavy smokers. COPD 4:339–346
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 (2009) Epigenetic profiles distinguish pleural mesothelioma from normal pleura and predict lung asbestos burden and clinical outcome. Cancer Res 69:227–234
Clin B, Paris C, Ameille J, Brochard P, Conso F, Gislard A, Laurent F, Letourneux M, Luc A, Schorle E, Pairon JC (2011) Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in the absence of pulmonary fibrosis? Thorax 66:985–991
Comar M, Zanotta N, Bonotti A, Tognon M, Negro C, Cristaudo A, Bovenzi M (2014) Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area. PLoS One 9:e104848
Comar M, Zanotta N, Zanconati F, Cortale M, Bonotti A, Cristaudo A, Bovenzi M (2016) Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma. Lung Cancer 94:61–67
Courtice MN, Wang X, Lin S, Yu IT, Berman DW, Yano E (2016) Exposure–response estimate for lung cancer and asbestosis in a predominantly chrysotile-exposed Chinese factory cohort. Am J Ind Med 59:369–378
Dammann R, Strunnikova M, Schagdarsurengin U, Rastetter M, Papritz M, Hattenhorst UE, Hofmann HS, Silber RE, Burdach S, Hansen G (2005) CpG island methylation and expression of tumour-associated genes in lung carcinoma. Eur J Cancer 41:1223–1236
De Prins S, Koppen G, Jacobs G, Dons E, Van de Mieroop E, Nelen V, Fierens F, Int PL, De Boever P, Cox B, Nawrot TS, Schoeters G (2013) Influence of ambient air pollution on global DNA methylation in healthy adults: a seasonal follow-up. Environ Int 59:418–424
Diandini R, Takahashi K, Park EK, Jiang Y, Movahed M, Le GV, Lee LJ, Delgermaa V, Kim R (2013) Potential years of life lost (PYLL) caused by asbestos-related diseases in the world. Am J Ind Med 56:993–1000
Dogan MV, Shields B, Cutrona C, Gao L, Gibbons FX, Simons R, Monick M, Brody GH, Tan K, Beach SR, Philibert RA (2014) The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics 15:151
Dujic Z, Eterovic D, Tocilj J (1993) Association between asbestos-related pleural plaques and resting hyperventilation. Scand J Work Environ Health 19:346–351
Fan T, Fang SC, Cavallari JM, Barnett IJ, Wang Z, Su L, Byun HM, Lin X, Baccarelli AA, Christiani DC (2014) Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study. BMC Public Health 14:1279
Forouzanfar MH, Alexander L, Anderson HR et al (2015) Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet 386:2287–2323
Guerra S, Halonen M, Vasquez MM et al (2015) Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. Lancet. Respir Med 3:613–620
Guerrero-Preston R, Goldman LR, Brebi-Mieville P, Ili-Gangas C, Lebron C, Witter FR, Apelberg BJ, Hernández-Roystacher M, Jaffe A, Halden RU, Sidransky D (2010) Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds. Epigenetics 5:539–546
Helling BA, Yang IV (2015) Epigenetics in lung fibrosis: from pathobiology to treatment perspective. Curr Opin Pulm Med 21:454–462
Helmig S, Aliahmadi N, Schneider J (2010) Tumour necrosis factor-alpha gene polymorphisms in asbestos-induced diseases. Biomarkers 15:400–409
Kasuga I, Yonemaru M, Kiyokawa H, Ichinose Y, Toyama K (1996) Clinical evaluation of serum type IV collagen 7 S in idiopathic pulmonary fibrosis. Respirology 1:277–281
Kile ML, Fang S, Baccarelli AA, Tarantini L, Cavallari J, Christiani DC (2013) A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders. Environ Health 12:47
Kodama N, Yamaguchi E, Hizawa N, Furuya K, Kojima J, Oguri M, Takahashi T, Kawakami Y (1998) Expression of RANTES by bronchoalveolar lavage cells in nonsmoking patients with interstitial lung diseases. Am J Respir Cell Mol Biol 18:526–531
Kopylev L, Christensen KY, Brown JS, Cooper GS (2015) A systematic review of the association between pleural plaques and changes in lung function. Occup Environ Med 72:606–614
Kotani K, Kawabata I, Mu H, Kurozawa Y, Itoh Y (2007) Urinary protein 1/Clara cell 16 concentrations and lung functions in male subjects with pneumoconiosis. Ann Clin Biochem 44:560–562
Lange NE, Sordillo J, Tarantini L, Bollati V, Sparrow D, Vokonas P, Zanobetti A, Schwartz J, Baccarelli A, Litonjua AA, DeMeo DL (2012) Alu and LINE-1 methylation and lung function in the normative ageing study. BMJ Open 2:e1231
Larson TC, Lewin M, Gottschall EB, Antao VC, Kapil V, Rose CS (2012) Associations between radiographic findings and spirometry in a community exposed to Libby amphibole. Occup Environ Med 69:361–366
Leeming DJ, Sand JM, Nielsen MJ, Genovese F, Martinez FJ, Hogaboam CM, Han MK, Klickstein LB, Karsdal MA (2012) Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis. Biomark Insights 7:119–126
Lepeule J, Baccarelli A, Tarantini L, Motta V, Cantone L, Litonjua AA, Sparrow D, Vokonas PS, Schwartz J (2012) Gene promoter methylation is associated with lung function in the elderly: The normative aging study. Epigenetics 7:261–269
Lepeule J, Bind MC, Baccarelli AA, Koutrakis P, Tarantini L, Litonjua A, Sparrow D, Vokonas P, Schwartz JD (2014) Epigenetic influences on associations between air pollutants and lung function in elderly men: the normative aging study. Environ Health Perspect 122:566–572
Loth DW, Artigas MS, Gharib SA et al (2014) Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nat Genet 46:669–677
Madrigano J, Baccarelli AA, Mittleman MA, Sparrow D, Vokonas PS, Tarantini L, Schwartz J (2014) Aging and epigenetics: longitudinal changes in gene-specific DNA methylation. Epigenetics 7:63–70
Mastrangelo G, Marangi G, Ballarin MN et al (2013) Post-occupational health surveillance of asbestos workers. Med Lav 104:351–358
Mesaros C, Worth AJ, Snyder NW, Christofidou-Solomidou M, Vachani A, Albelda SM, Blair IA (2015) Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure. Bioanalysis 7:1157–1173
Miller A, Warshaw R, Nezamis J (2013) Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening. Am J Ind Med 56:1383–1393
Mossman BT, Lippmann M, Hesterberg TW, Kelsey KT, Barchowsky A, Bonner JC (2011) Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos. J Toxicol Environ Health B Crit Rev 14:76–121
Mutsaers SE, Harrison NK, McAnulty RJ, Liao JY, Laurent GJ, Musk AW (1998) Fibroblast mitogens in bronchoalveolar lavage (BAL) fluid from asbestos-exposed subjects with and without clinical evidence of asbestosis: no evidence for the role of PDGF, TNF-alpha, IGF-1, or IL-1 beta. J Pathol 185:199–203
Park EK, Yates DH, Wilson D (2014) Lung function profiles among individuals with nonmalignant asbestos-related disorders. Saf Health Work 5:234–237
Partanen R, Koskinen H, Hemminki K (1995) Tumour necrosis factor-alpha (TNF-alpha) in patients who have asbestosis and develop cancer. Occup Environ Med 52:316–319
Petrek M, Hermans C, Kolek V, Fialova J, Bernard A (2002) Clara cell protein (CC16) in serum and bronchoalveolar lavage fluid of subjects exposed to asbestos. Biomarkers 7:58–67
Pirela SV, Lu X, Miousse I, Sisler JD, Qian Y, Guo N, Koturbash I, Castranova V, Thomas T, Godleski J, Demokritou P (2016) Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: a case study of toxicological implications from nanomaterials released during consumer use. NanoImpact 1:1–8
Prince P, Boulay ME, Page N, Desmeules M, Boulet LP (2008) Induced sputum markers of fibrosis and decline in pulmonary function in asbestosis and silicosis: a pilot study. Int J Tuberc Lung Dis 12:813–819
Rava M, Le Moual N, Dumont X, Guerra S, Siroux V, Jacquemin B, Kauffmann F, Bernard A, Nadif R (2015) Serum club cell protein 16 is associated with asymptomatic airway responsiveness in adults: Findings from the French epidemiological study on the genetics and environment of asthma. Respirology 20:1198–1205
Ruiz-Hernandez A, Kuo C, Rentero-Garrido P, Tang W, Redon J, Ordovas JM, Navas-Acien A, Tellez-Plaza M (2015) Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence. Clin Epigenetics 7:55
Soler Artigas M, Wain LV, Repapi E et al (2011) Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function. Am J Respir Crit Care Med 184:786–795
Świątkowska B, Wojciech S, Szubert Z, Szeszenia-Dąbrowska N (2014) Continued spirometry changes after cessation of exposure in asbestos-cement workers. J Occup Environ Med 56:403–408
Tellez-Plaza M, Tang W, Shang Y et al (2014) Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 122:946–954
Vehmas T, Pallasaho P, Piirila P (2013) Lung function predicts mortality: 10-year follow-up after lung cancer screening among asbestos-exposed workers. Int Arch Occup Environ Health 86:667–672
Wang X, Wang M, Qiu H, Yu I, Yano E (2010) Longitudinal changes in pulmonary function of asbestos workers. J Occup Health 52:272–277
Wilken D, Velasco GM, Manuwald U, Baur X (2011) Lung function in asbestos-exposed workers, a systematic review and meta-analysis. J Occup Med Toxicol 6:21
Winters CA, Hill WG, Rowse K, Black B, Kuntz SW, Weinert C (2012) Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos. BMJ Open 2:e001552
Yang X, Yuan Y, Lu X, Yang J, Wang L, Song J, Nie J, Zhang Q, Niu Q (2015) The relationship between cognitive impairment and global DNA methylation decrease among aluminum potroom workers. J Occup Environ Med 57:713–717
Yoo S, Takikawa S, Geraghty P, Argmann C, Campbell J, Lin L, Huang T, Tu Z, Foronjy RF, Spira A, Schadt EE, Powell CA, Zhu J (2015) Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD. PLoS Genet 11:e1004898
Yu M, Zhang Y, Jiang Z, Chen J, Liu L, Lou J, Zhang X (2015) Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population. Environ Health Prev Med 20:369–378
Zhu Z, Hou L, Bollati V et al (2012) Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol 41:126–139
Acknowledgements
This work was financially supported by the grants from the Health and Family Planning Commission of Zhejiang Province (2015ZDA010, 2015KYA058, 2016KYB074), and the Project of Zhejiang Province Science and Technology Plan (2013F20004, 2014C03030). The contents of this article do not necessarily reflect the views of its sponsors, nor do they necessarily reflect the views and policies of the sponsors.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Yu, M., Lou, J., Xia, H. et al. Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population. Int Arch Occup Environ Health 90, 265–274 (2017). https://doi.org/10.1007/s00420-017-1195-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00420-017-1195-1