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

Seminar Infection Diseases in Arctic

High prevalence rates of chronic hepatitis B (CHB) have been reported in the Arctic countries. There is a strong epidemiological evidence of a causal relationship between persistent hepatitis B virus (HBV) infection and development of hepatocellular carcinoma (HCC). However, the factors contributing to over-replication of HBV and progression of HCC are not fully identified. Here, we suggest human burden 2,3,7,8-TCDD (TCDD) a trigger of HBV replication. Common view that viral diseases are secondary to the initial impact caused by marine food TCDD on human immune system failed, because the current body burden TCDD in the Arctic inhabitants is yet too low to impair human antiviral immunity. On the other hand, it was shown that human TCDD is capable to transcriptionally upregulate cancer-associated human viruses. This augmentation is the Ah receptor-mediated, dose-dependent, and relies on the amount of “dioxin response elements” (DRE) in viral gene promoter. Thus the HIV-1 has the only DRE, and is trans-activated with TCDD at dose about 15 times of the current body burden of general population, while the CMV, which possesses 10 DREs, is fully upregulated with TCDD at dose 20 times lower than body burden. As for the HBV, its gene promoter contains 4 DREs meaning that HBV might be upregulated in human liver cells by TCDD concentrations lower than 1.0 nM and higher than 0.3 pM shown for the HIV-1 and CMV, respectively. This estimated level is congruent with the current TCDD human body burden in the Arctic, i.e., ~ 3.0 ng/kg (lipid). Understanding of the Ah receptor-mediated trigger mode of TCDD action on viral gene endorses evaluation of the role of body TCDD in the development of HBV-associated CHB and HCC in immunocompetent people. From this mechanistic standpoint, effective treatment tools could be sought among TCDD antagonists for binding at the Ah receptor, and inhibitors, which block transcriptional complex binding to the viral DREs. These antagonists/inhibitors include already used medicines like salycilamide, as well as some natural compounds like coplanar bioflavonoids in green tea, etc.

Note. Abstracts are published in author's edition

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