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Jennifer A. Rusiecki,¹ Andrea Baccarelli,² Valentina Bollati,² Letizia Tarantini,² Lee E. Moore,³ and Eva C. Bonefeld-Jorgensen⁴

¹Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; ²Department of Environmental and Occupational Health, University of Milan and IRCCS Maggiore Hospital, Regina Elena and Mangiagalli, Center of Molecular and Genetic Epidemiology, Milan, Italy; ³Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; ⁴University of Aarhus, Unit of Cellular and Molecular Toxicology, Centre of Arctic Environmental Medicine, Institute of Public Health, University of Aarhus, Aarhus, Denmark

Abstract
Background: Persistent organic pollutants (POPs) may influence epigenetic mechanisms ; therefore, they could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide.

Objective: Our aim in this study was to evaluate the relationship between plasma POPs concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPs.

Methods: We used pyrosequencing to estimate global DNA methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses.

Results: We found inverse correlations between percents methylcytosine and many of the POP concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically significant inverse linear relationships mainly for the Alu assay for p,p΄-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane ; β = –0.26) , p,p΄-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene ; β = –0.38], β-hexachlorocyclohexane (β = –0.48) , oxychlordane (β = –0.32) , α-chlordane (β = -0.75) , mirex (β = –0.27) , sum of polychlorinated biphenyls (β = –0.56) , and sum of all POPs (β = –0.48) . Linear regressions for the LINE-1 assay showed β estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant.

Conclusions: This is the first study to investigate environmental exposure to POPs and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPs and merit further investigation.

Key words: DNA methylation, global methylation, Greenland, hypomethylation, Inuit, organochlorines, PCBs, persistent organic pollutants, pesticides, polychlorinated biphenyls, POPs, serum. Environ Health Perspect 116:1547–1552 (2008) .  doi:10.1289/ehp.11338 available via http://dx.doi.org/ [Online 16 July 2008]

Address correspondence to J.A. Rusiecki, Department of Preventive Medicine and Biometrics, PMB Room A1039, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814–4799 USA. Telephone: (301) 295–3712. Fax: (301) 295–1854. E-mail: jrusiecki@usuhs.mil

This research was supported by a Uniformed Services University intramural start-up grant, RO87YT.

The authors declare they have no competing financial interests.

Received 6 February 2008 ; accepted 16 July 2008.