International Union for Circumpolar Health Ministry of Public Health and Social Development of RF Russian Academy of Medical Sciences Siberian Branch of Russian Academy of Medical Sciences Siberian Branch of Russian Academy of Sciences Medical Polar Fund “Science” The Northern Forum

Abstracts

Environmental health

Background: Gene-damaging agents have been a primary focus of cancer epidemiology; however, all xenobiotics do not interact with DNA directly. Some exogenous agents operate at the epigenetic level, meaning they have an influence on chromosomal stability and gene expression, not directly on changes in the DNA sequence. DNA methylation (both hypermethylation and hypomethylation) is an epigenetic mechanism which has been associated with cancer. In particular, global DNA hypomethylation can increase expression of genes that would normally be methylated and therefore silenced (e.g., oncogenes), while hypermethylation of the promoter region of certain genes, such as p16 and GSTp1, can silence these genes which would normally be expressed. Most pesticides and persistent organic pollutants (POPs) are good candidates for being epicarcinogens because they indirectly alter gene and protein expression patterns without directly interacting with the DNA. Greenlandic Inuit have some of the highest reported levels of POPs in the world, however, there is some variation among the population, which allows for stratification between high and lower levels.

Aim: We will evaluate percent of global DNA methylation (via Line-1 repetitive element assay) and percent methylation in the promoter regions of p16 and GSTp1 for 71 Greenlandic Inuit. We will compare participants with high exposures to those with lower exposures to investigate whether high exposure to specific POPs is associated with aberrant DNA methylation.

Methods: Whole blood specimens which have been collected from 71 Greenlandic Inuit under the Human Health Programme of Arctic Monitoring and Assessment Programme (AMAP) were previously analyzed for levels of the following POPs: β-hexachlorocyclohexane, chlordane (sum of -,-, cis-, nona-,trans-, and oxychlordanes) DDT (sum of DDT and DDE), hexachlorobenzene, mirex, sum of 14 PCB congeners, and toxaphene.a We will extract DNA from the whole blood samples. The method to quantify global DNA methylation is based on using bisulfite treatment of DNA and simultaneous PCR, followed by pyrosequencing. This is the first study to investigate DNA methylation patterns in a population with high exposures to specific POPs.

aDeutch and Hansen, 2000. High human plasma levels of organochlorine compounds in Greenland. Danish Medical Bulletin, Vol 47(2)132-137.

Note. Abstracts are published in author's edition

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