? ? Studies in vitro, studies in rodents, and some epidemiology studies suggest cancer preventing mechanisms of phytochemicals in green tea, which can be called an herb or a food. Yet, not one green tea human intervention study exists for cancer incidence, nor does much intervention data exist for pre-cancer biomarkers. In fact, it hasn't even been shown that a human green tea intervention can even impact the various anti-cancer defense mechanisms attributed to green tea (which should be a prerequisite to major studies on cancer incidence or pre-cancer biomarkers). Therefore, a project is proposed to test the following hypothesis: in young adult smokers, 6 weeks of 6 cups of green tea/d produces changes in bronchoalveolar lavage (BAL) samples related to improved anti- lung cancer defense mechanisms. This does not suppose that green tea can prevent lung cancer in smokers better than smoking cessation. However, the pre-cancer stress in smokers provides a chance to see changes in cancer risk-related parameters in a short time. Moreover, this lung cancer-relevant population allows use of BAL, a minimally invasive sampling of a site of potential cancer onset. Project end points relate to defenses against cancer development, and have shown changes due to green tea or its flavonoids in animals and/or in vitro, and can be measured in BAL samples, and in most cases, have shown abnormal BAL values in smokers. End points include: DNA adducts, ERK 1/2 phosphorylation, lysyl oxidase activity, two endogenous antioxidant defense molecules; neutrophil superoxide release; and TNF mRNA. This PI has worked with BAL samples, has access to smokers and BAL sampling via a collaborator MD, has rare experience with the lysyl oxidase assay, and possesses relevant preliminary data. Positive results in this project can lead to studies on tea or tea flavonoid supplements which examine pre-cancer biomarkers (ie DNA methylation), and ultimately, incidence of lung and other cancers. Negative results will justify re-evaluation of how to study green tea for chemoprevention.Green tea may produce body effects that help prevent cancer, but human studies haven't fully shown this yet. This project looks for these effects in smokers using a wash sample from lungs, a site where cancer can occur in smokers. Although green tea may not prevent lung cancer in all smokers, this group is good to study since they can show changes in cancer relevant measures faster than other people ? ? ?
