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

The development of malignancies in Arctic peoples is usually linked to some common viruses, such as human papilloma virus (HPV) (cervical cancer) and Epstein-Barr virus (EBV) (nasopharyngeal cancer and lymphoproliferative diseases). As Arctic populations are exposed to persistent organic pollutants through the traditional diet including sea mammal fat, it is thought that these pollutants, among those 2,3,7,8-TCDD (dioxin) is the most potent one, impact key elements of the immune system thereby compromising the human antiviral defense. However, although in some groups the body burden of dioxin is close to that impairing immune system in laboratory animals, the dietary exposure to dioxin is too low to impact antiviral immunity in humans. Here, a direct transcriptional mechanism is suggested how body burden dioxin might activate replication of common viruses associated with specific malignancies. The data already revealed are: 1) human common viruses possess “dioxin response elements” (DRE) in 5’-upstream region of viral gene; 2) containing the only DRE HIV-1 is trans-activated with dioxin concentration about 15 times of its human body burden; 3) human cytomegalovirus possesses 10 promoter DREs, and is up-regulated with dioxin dose about 30 times lower than body burden. 4) virus augmentation with dioxin is always mediated by dioxin-specific Ah receptor in the target human cells. According to “Species DRE Summary”, the HPV has a single DRE in gene promoter, while the EBV possesses 22 DREs in gene 5’-upstream region. Therefore, increasing rate of HPV-associated cervical cancer is expected in women with the highest body burden dioxin in general population residing in the Arctic. However, the general body burden (~ 3.0 ng/kg, lipid) is enough to trigger transcriptional up-regulation of multiple DREs-containing EBV, which leads to the development of EBV-associated malignancies. The individual dioxin/EBV/cancer risk assessment might be dependent on the amount of human Ah receptor, and its binding affinity to dioxin, which varies ~ 20-fold. Newly discovered role of body burden dioxin should be considered in epidemiological studies and risk-assessment profiles critical to virus-associated cancer diseases prevention and control in the Arctic.

Note. Abstracts are published in author's edition

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Last update: 06-Jul-2012 (11:52:05)