Environmental carcinogens such as polycyclic aromatic hydrocarbons (PAH), which are present in cigarette smoke can bind to DNA to form DNA adducts (additional products), which may lead to mutations in critical genes, eventually leading to cancer. A positive correlation between PAH-DNA adducts and tumor incidence was observed by us (Arch Toxicol, 2015). Epidemiological data show that people with higher levels of PAH-DNA adducts are 2-3 times more to have lung cancer in the future than those with lower adduct levels. Therefore, reduction of DNA adduct levels may decrease risk of lung cancer. We discovered that dietary fish oil that contains omega-3 fatty acids decreased lung and liver DNA addu...

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Environmental carcinogens such as polycyclic aromatic hydrocarbons (PAH), which are present in cigarette smoke can bind to DNA to form DNA adducts (additional products), which may lead to mutations in critical genes, eventually leading to cancer. A positive correlation between PAH-DNA adducts and tumor incidence was observed by us (Arch Toxicol, 2015). Epidemiological data show that people with higher levels of PAH-DNA adducts are 2-3 times more to have lung cancer in the future than those with lower adduct levels. Therefore, reduction of DNA adduct levels may decrease risk of lung cancer. We discovered that dietary fish oil that contains omega-3 fatty acids decreased lung and liver DNA adducts in mice by 30-45% after PAH treatment (PLoS One, 2011). We also found that pure omega-3 eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) significantly attenuate incidence of lung cancer in mice treated with the PAH benzo[a]pyrene, a human carcinogen. Several P450 enzymes may metabolize omega-3 fatty acids to their epoxy metabolites that inhibit tumor formation, tumor growth and metastasis. However, the mechanisms by which omega-3 fatty acids prevent cancer are not fully understood. The central hypothesis of this application is that omega 3-fatty acids will inhibit pulmonary carcinogenesis by multiple mechanisms entailing attenuation of PAH-DNA adduct formation, and by suppression of tumorigenesis, probably via epoxy metabolites of omega-3 fatty acids. If our hypothesis turns out to be correct, then it will break new grounds in the current understanding of cancer prevention. The proposed studies should lead to novel strategies against cancers caused by environmental carcinogens. Cancer prevention is a very important anticancer strategy, especially in high risk populations such as smokers and others exposed to environmental carcinogens. We are optimistic that the proposed research will be paradigm shifting and will lead to novel strategies for cancer prevention.

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