Mechanisms Of Inactivation Of PETN By Carchnoqen Benzo(a) Pyrene

Epidemiologic studies show that only 5 - 10% of cancer cases are direcctlyinduced by genetic deficiency, while 90-95% of all cases are associated withenvironmental pollution. For example, 87% of lung cancer is mainly caused bysmoking, and the "cancer villages" in recent years is an extreme example of cancercaused by environmental pollution. Polycyclic aromatic hydrocarbons (PAHs) arewide spread environmental carcinogens that can induce DNA damage, but the precisemechanisms of action of PAH in causing cancers remain obscure. In our pilot study,we investigated the effects of BaP, a representative of PAHs, on the human bronchialepithelial cells and based on that, we try to elucidate the molecular mechanisms ofenvironmental pollution related cancer. The results showed that BaP treatmentaffected cell morphology and activated the PI3K/AKT signaling pathway.Interestingly, of the tumor suppressor PTEN was markedly downregulated at proteinand mRNA levels, while the DNA methyltransferases (DNMT1) was drasticallyunregulated. We are still investigating the detailed mechanisms underlyingBaP-modulated expression of PTEN and DNMT1. Our work would shed new insightsinto the molecular mechanisms of environmental pollution related cancer, and providenovel strategies for prevention and treatment of this deadly disease.