Green Tea Anticancer Mechanisms in Smokers

描述（由申请人提供）： 体外研究，啮齿动物研究和一些流行病学研究表明绿色茶中的植物化学物质具有预防癌症的机制，绿茶可以被称为草药或食物。然而，没有一个绿色茶人类干预研究存在癌症发病率，也没有太多的干预数据存在癌前生物标志物。事实上，甚至还没有证据表明，人类绿色茶的干预甚至可以影响绿色茶的各种抗癌防御机制（这应该是癌症发病率或癌前生物标志物的主要研究的先决条件）。因此，提出了一个项目来检验以下假设：在年轻的成年吸烟者中，6周6杯绿色茶/d产生与改善的抗肺癌防御机制相关的支气管肺泡灌洗（BAL）样品的变化。这并不意味着绿色茶比戒烟更能预防吸烟者患肺癌。然而，吸烟者的癌前压力提供了一个在短时间内看到癌症风险相关参数变化的机会。此外，该肺癌相关人群允许使用BAL，这是一种对潜在癌症发作部位的微创采样。项目终点涉及对癌症发展的防御，并且已经在动物和/或体外显示出由于绿色茶或其黄酮类化合物的变化，并且可以在BAL样品中测量，并且在大多数情况下，已经在吸烟者中显示出异常的BAL值。终点包括：DNA加合物、ERK 1/2磷酸化、赖氨酰氧化酶活性、两种内源性抗氧化防御分子、中性粒细胞超氧化物释放和TNF mRNA。该PI曾使用BAL样本，可通过合作者MD接触吸烟者和BAL采样，具有赖氨酰氧化酶试验的罕见经验，并拥有相关的初步数据。该项目的积极结果可以导致对茶或茶类黄酮补充剂的研究，这些研究可以检查癌前生物标志物（即DNA甲基化），并最终检查肺癌和其他癌症的发病率。负面的结果将证明重新评估如何研究绿色茶的化学预防作用。绿色茶可能会产生身体效应，有助于预防癌症，但人类研究还没有充分表明这一点。该项目使用来自肺部的洗涤样本寻找吸烟者的这些影响，肺部是吸烟者可能发生癌症的部位。虽然绿色茶可能不能预防所有吸烟者的肺癌，但这一组是很好的研究，因为他们可以比其他人更快地显示癌症相关措施的变化

DESCRIPTION (provided by applicant): 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