A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an individual basis have not yet been studied. Moreover, current evidence shows that environmental exposure could generate changes in DNA methylation settings and, subsequently, the function of genes. In this study, we analyzed the effect of chronic exposure to nanoparticles (NP) in occupationally exposed workers repeatedly sampled in four consecutive years (2016-2019). A detailed methylation pattern analysis of 14 persons (10 exposed and 4 controls) was performed on an individual basis. A microarray-based approach using chips, allowing the assessment of more than 850 K CpG loci, was used. Individual DNA methylation patterns were compared by principal component analysis (PCA). The results show the shift in DNA methylation patterns in individual years in all the exposed and control subjects. The overall range of differences varied between the years in individual persons. The differences between the first and last year of examination (a three-year time period) seem to be consistently greater in the NP-exposed subjects in comparison with the controls. The selected 14 most differently methylated cg loci were relatively stable in the chronically exposed subjects. In summary, the specific type of long-term exposure can contribute to the fixing of relevant epigenetic changes related to a specific environment as, e.g., NP inhalation.

Department of Aerosol Chemistry and Physics Institute of Chemical Process Fundamentals CAS Rozvojova 1 165 02 Prague 6 Czech Republic

Department of Genetic Toxicology and Epigenetics Institute of Experimental Medicine CAS Videnska 1083 142 20 Prague 4 Czech Republic

Department of Machining and Assembly Department of Engineering Technology Department of Material Science Faculty of Mechanical Engineering Technical University in Liberec Studentska 1402 2 461 17 Liberec Czech Republic

Department of Nanotoxicology and Molecular Epidemiology Institute of Experimental Medicine CAS Videnska 1083 142 20 Prague 4 Czech Republic

Department of Occupational Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Na Bojisti 1 120 00 Prague 2 Czech Republic

Experimental Medicine Centre Institute for Clinical and Experimental Medicine Videnska 1958 9 140 21 Prague 4 Czech Republic

Zobrazit více v PubMed

Waddington C.H. The epigenotype. Endeavour. 1942;1:18–20. doi: 10.1093/ije/dyr184. PubMed DOI

Waddington C.H. The Basic Ideas of Biology. Edinburgh University Press; Edinburgh, UK: 1968. Towards a Theoretical Biology; pp. 1–32.

Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21. doi: 10.1101/gad.947102. PubMed DOI

Lövkvist C., Dodd I.B., Sneppen K., Haerter J.O. DNA methylation in human epigenomes depends on local topology of CpG sites. Nucleic Acids Res. 2016;44:5123–5132. doi: 10.1093/nar/gkw124. PubMed DOI PMC

Kanherkar R.R., Bhatia-Dey N., Csoka A.B. Epigenetics across the human lifespan. Front. Cell Dev. Biol. 2014;2:49. doi: 10.3389/fcell.2014.00049. PubMed DOI PMC

Ferrari L., Carugno M., Bollati V. Particulate matter exposure shapes DNA methylation through the lifespan. Clin. Epigenetics. 2019;11:129. doi: 10.1186/s13148-019-0726-x. PubMed DOI PMC

Field A.E., Robertson N.A., Wang T., Havas A., Ideker T., Adams P.D. DNA Methylation Clocks in Aging: Categories, Causes, and Consequences. Mol. Cell. 2018;71:882–895. doi: 10.1016/j.molcel.2018.08.008. PubMed DOI PMC

Xiao F.-H., Wang H.-T., Kong Q.-P. Dynamic DNA Methylation during Aging: A “Prophet” of Age-Related Outcomes. Front. Genet. 2019;10:107. doi: 10.3389/fgene.2019.00107. PubMed DOI PMC

Jung S.-E., Shin K.-J., Lee H.Y. DNA methylation/based age prediction from various tissues and body fluids. BMB Rep. 2017;50:546–553. doi: 10.5483/BMBRep.2017.50.11.175. PubMed DOI PMC

Sanz L.A., Kota S.A., Feil R. Genome-wide DNA demethylation in mammals. Genome Biol. 2010;11:1–4. doi: 10.1186/gb-2010-11-3-110. PubMed DOI PMC

Seisenberger S.J., Peat R., Hore T.A., Santos F., Dean W., Reik W. Reprogramming DNA methylation in the mammalian life cycle: Building and breaking epigenetic barriers. Philos. Trans. R. Soc. B. 2013;368:20110330. doi: 10.1098/rstb.2011.0330. PubMed DOI PMC

Luo C., Hajkova P., Ecker J.R. Dynamic DNA methylation: In the right place at the right time. Science. 2018;361:1336–1340. doi: 10.1126/science.aat6806. PubMed DOI PMC

Szyf M. The Implication of DNA Methylation for Toxicology: Toward Toxicomethylomics, the Toxicology of DNA Methylation. Toxicol. Sci. 2011;120:235–255. doi: 10.1093/toxsci/kfr024. PubMed DOI PMC

Tobi E.W., Slieker R.C., Stein A.D., Suchiman H.E., Slagboom P.E., van Zwet E.W., Heijmans B.T., Lumey L.H. Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome. Int. J. Epidemiol. 2015;44:1211–1223. doi: 10.1093/ije/dyv043. PubMed DOI PMC

Bateson P., Gluckman P., Hanson M. The biology of developmental plasticity and the predictive adaptive response hypothesis. J. Physiol. 2014;592:2357–2368. doi: 10.1113/jphysiol.2014.271460. PubMed DOI PMC

Tsang S.-Y., Ahmad T., Mat F.W.K., Zhao C., Xiao S., Xia K., Xue H. Variation of global DNA methylation levels with age and in autistic children. Human Genom. 2016;10:1–6. doi: 10.1186/s40246-016-0086-y. PubMed DOI PMC

Edwards T.M., Myers J.P. Environmental Exposures and Gene Regulation in Disease Etiology. Environ. Health Perspect. 2007;115:1264–1270. doi: 10.1289/ehp.9951. PubMed DOI PMC

Weidman J.R., Dolinoy D.C., Murphy S.K., Jirtle R.L. Cancer Susceptibility: Epigenetic Manifestation of Environmental Exposures. Cancer J. 2007;13:9–16. doi: 10.1097/PPO.0b013e31803c71f2. PubMed DOI

Rossnerova A., Honkova K., Pelclova D., Zdimal V., Hubacek J.A., Chvojkova I., Vrbova K., Rossner P., Jr., Topinka J., Vlckova S., et al. DNA methylation profiles in a group of workers occupationally exposed to nanoparticles. Int. J. Mol. Sci. 2020;21:2420. doi: 10.3390/ijms21072420. PubMed DOI PMC

Markunas C.A., Xu Z., Harlid S., Wade P.A., Lie R.T., Taylor J.A., Wilcox A.J. Identification of DNA Methylation Changes in Newborns Related to Maternal Smoking during Pregnancy. Environ. Health Perspect. 2014;122:1147–1153. doi: 10.1289/ehp.1307892. PubMed DOI PMC

Heijmans B.T., Tobi E.W., Stein A.D., Putter H., Blauw G.J., Susser E.S., Slagboom E.P., Lumey L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. USA. 2008;105:17046–17049. doi: 10.1073/pnas.0806560105. PubMed DOI PMC

Van Roekel E.H., Dugué P.-A., Jung C.-H., Joo J.-E., Makalic E., Wong E.M., English D.R., Southey M.C., Giles G.G., Lynch B.M., et al. Physical Activity, Television Viewing Time and DNA Methylation in Peripheral Blood. Med. Sci. Sports Exerc. 2019;51:490–498. doi: 10.1249/MSS.0000000000001827. PubMed DOI

Rossnerova A., Tulupova E., Tabashidze N., Schmuczerova J., Dostal M., Rossner P., Jr., Gmuender H., Sram R.J. Factor affecting the 27K DNA methylation pattern in asthmatic and healthy children from locations with various environments. Mutat. Res. 2013;741-742:18–26. doi: 10.1016/j.mrfmmm.2013.02.003. PubMed DOI

Ladd-Acosta C.H., Feinberg J.I., Brown S.C., Lurmann F.W., Croen L.A., Hertz-Picciotto I., Newschaffer C.J., Freinberg A.P., Fallin M.D., Volk H.E. Epigenetic marks of prenatal air pollution exposure found in multiple tissues relevant for child health. Environ. Int. 2019;126:363–376. doi: 10.1016/j.envint.2019.02.028. PubMed DOI PMC

Rider C.F., Carlsten C. Air pollution and DNA methylation: Effects of exposure in humans. Clin. Epigenet. 2019;11:131. doi: 10.1186/s13148-019-0713-2. PubMed DOI PMC

Yu X., Zhao B., Su Y., Zhang Y., Chen J., Wu W., Cheng Q., Guo X., Zhao Z., Ke X., et al. Association of prenatal organochlorine pesticide-dichlorodiphenyltrichloroethane exposure with fetal genome-wide DNA methylation. Life Sci. 2018;200:81–86. doi: 10.1016/j.lfs.2018.03.030. PubMed DOI

Van Der Plaat D.A., De Jong K., De Vries M., Van Diemen C.C., Nedeljkovic I., Amin N., Kromhout H., Vermeulen R.C.H., Postma D.S., Van Duijn C.M., et al. Occupational exposure to pesticides is associated with differential DNA methylation. Occup. Environ. Med. 2018;75:427–435. doi: 10.1136/oemed-2017-104787. PubMed DOI PMC

Zeng Z., Huo X., Zhang Y., Hylkema M.N., Wu Y., Xu X. Differential DNA methylation in newborns with maternal exposure to heavy metals from an e-waste recycling area. Environ. Res. 2019;171:536–545. doi: 10.1016/j.envres.2019.01.007. PubMed DOI

Liou S.H., Wu W.T., Liao H.Y., Chen C.Y., Tsai C.Y., Jung W.T., Lee H.L. Global DNA methylation and oxidative stress biomarkers in workers exposed to metal oxide nanoparticles. J. Hazard. Mater. 2017;331:329–335. doi: 10.1016/j.jhazmat.2017.02.042. PubMed DOI

Martins J., Czamara D., Sauer S., Rex-Haffner M., Dittrich K., Dörr P., de Punder K., Overfeld J., Knop A., Dammering F., et al. Childhood adversity correlates with stable changes in DNA methylation trajectories in children and converges with epigenetic signatures of prenatal stress. Neurobiol. Stress. 2021;15:1–13. doi: 10.1016/j.ynstr.2021.100336. PubMed DOI PMC

Aronica L., Levine A.J., Brennan K., Mi J., Gardner C., Haile R.W., Hitchins M.P. A systematic review of studies of DNA methylation in the context of a weight loss intervention. Epigenomics. 2017;9:769–787. doi: 10.2217/epi-2016-0182. PubMed DOI

Öner D., Ghosh M., Bové H., Moisse M., Boeckx B., Duca R.C., Poels K., Luyts K., Putzeys E., Landuydt K.V., et al. Differences in MWCNT- and SWCNT- induced DNA methylation alterations in association with the nuclear deposition. Part. Fibre Toxicol. 2018;15:1–19. doi: 10.1186/s12989-018-0244-6. PubMed DOI PMC

Moran S., Arribas C., Esteller M. Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences. Epigenomics. 2016;8:389–399. doi: 10.2217/epi.15.114. PubMed DOI PMC

Belli M., Tabocchini M.A. Ionizing Radiation-Induced Epigenetic Modifications and Their Relevance to Radiation Protection. Int. J. Mol. Sci. 2020;21:e5993. doi: 10.3390/ijms21175993. PubMed DOI PMC

Rossnerova A., Pokorna M., Svecova V., Sram R.J., Topinka J., Zölzer F., Rossner P., Jr. Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and “omics” biomonitoring studies and possible mechanisms. Mutat. Res. 2017;773:188–203. doi: 10.1016/j.mrrev.2017.07.002. PubMed DOI

Rossnerova A., Izzotti A., Pulliero A., Bast A., Rattan S.I.S., Rossner P., Jr. The molecular mechanisms of adaptive response related to the environmental stress. Int. J. Mol. Sci. 2020;21:7053. doi: 10.3390/ijms21197053. PubMed DOI PMC

Giuliani C., Bacalini M.G., Sazzini M., Pirazzini C., Franceschi C., Garagnani P., Luiselli D. The epigenetic side of human adaptation: Hypotheses, evidences and theories. Ann. Hum. Biol. 2015;42:1–9. doi: 10.3109/03014460.2014.961960. PubMed DOI

Vineis P., Chatziioannou A., Cunliffe V.T., Flanagan J.M., Hanson M., Kirsch-Volders M., Kyrtopoulos S. Epigenetic memory in response to environmental stressors. FASEB J. 2017;31:2241–2251. doi: 10.1096/fj.201601059RR. PubMed DOI

Hoang T.T., Sikdar S., Xu C.-J., Lee M.K., Cardwell J., Forno E., Imboden M., Jeong A., Madore A.-M., Qi C., et al. Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study. Eur. Respir. J. 2020;56:1–187. doi: 10.1183/13993003.00217-2020. PubMed DOI PMC

Cortesi E., Ventura J.J. Lgr6: From Stemness to Cancer Progression. J. Lung Health Dis. 2019;3:12–15. doi: 10.29245/2689-999X/2018/1.1144. PubMed DOI PMC

Raslan A.A., Yoon J.K. R-spondins: Multi-mode WNT signaling regulators in adult stem cells. Int. J. Biochem. Cell Biol. 2019;106:26–34. doi: 10.1016/j.biocel.2018.11.005. PubMed DOI

Moszcyński P., Rutowski J., Słowiński S., Bern S., Jakus-Stoga D. Effects of occupational exposure to mercury vapors on T-cell and NK-cell populations. Arch. Med. Res. Winter. 1996;27:503–507. PubMed

Guo J.U., Su Y., Zhong C., Ming G., Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145:423–434. doi: 10.1016/j.cell.2011.03.022. PubMed DOI PMC

Talbot N., Kubelova L., Makes O., Ondracek J., Cusack M., Schwarz J., Vodicka P., Zikova N., Zdimal V. Transformations of aerosol particles from an outdoor to indoor environment. Aerosol Air Qual. Res. 2017;17:653–665. doi: 10.4209/aaqr.2016.08.0355. DOI

Pelclova D., Zdimal V., Schwarz J., Dvorackova S., Komarc M., Ondracek J., Kostejn M., Kacer P., Vlckova S., Fenclova Z., et al. Markers of oxidative stress in the exhaled breath condensate of workers handling nanocomposites. Nanomaterials. 2018;8:611. doi: 10.3390/nano8080611. PubMed DOI PMC

Pelclova D., Zdimal V., Komarc M., Schwarz J., Ondracek J., Ondrackova L., Kostejn M., Vlckova S., Fenclova Z., Dvorackova S., et al. Three-Year Study of Markers of Oxidative Stress in Exhaled Breath Condensate in Workers Producing Nanocomposites, Extended by Plasma and Urine Analysis in Last Two Years. Nanomaterials. 2020;10:2440. doi: 10.3390/nano10122440. PubMed DOI PMC

Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215. doi: 10.1093/nar/16.3.1215. PubMed DOI PMC

Aryee M.J., Jaffe A.E., Corrada-Bravo H., Ladd-Acosta C., Feinberg A.P., Hansen K.D., Irizarry R.A. Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–1369. doi: 10.1093/bioinformatics/btu049. PubMed DOI PMC

McCartney D.L., Walker R.M., Morris S.W., McIntosh A.M., Porteous D.J., Evans K.L. Identification of polymorphic and off-target probe binding sites on the Illumina Infinium MethylationEPIC BeadChip. Genom. Data. 2016;9:22–24. doi: 10.1016/j.gdata.2016.05.012. PubMed DOI PMC

Houseman W.P., Accomando W.P., Koestler D.C., Christensen B.C., Marsit C.J., Nelson H.H., Wiencke J.K., Kelsey K.T. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinform. 2012;13:86. doi: 10.1186/1471-2105-13-86. PubMed DOI PMC

Armstrong N., Mather K.A., Thalamuthu A., Wright M.J., Trollor J.N., Ames D., Brodaty H., Schofield P.R., Sachdev P.S., Kwok J.B. Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks. Epigenomics. 2017;9:689–700. doi: 10.2217/epi-2016-0179. PubMed DOI

Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution