There are several reasons to believe NF-kB is a good target by which to examine CS-induced lung cancer development and its chemoprevention. First, benzo[a]pyrene, a component of CS, has recently been shown to activate NF-kB in lung adenocarcinoma cells (37) and in vascular smooth muscle cells (50). Second, CS is also a potent source of ROIs (44-46), which are required for NF-kB activation (47). Our laboratory and others have shown that antioxidants and overexpression of cells with antioxidant enzymes such as Mn superoxide dismutase or with y-glutamylcysteinyl synthase (51-53) block NF-kB activation. Third, NF-kB activation has been implicated in chemical carcinogenesis and tumorigenesis (54,55). Fourth, CS has been shown to induce NF-KB-regulated chemokine genes in bronchial epithelium (Ref. 38 and references therein). Lastly our laboratory and others have shown that most chemopreventive agents suppress NF-kB activation (56-60).
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