Detoxication of Air Pollutants in Humans with a Broccoli Supplement

 描述（由申请人提供）：空气污染最近被IARC宣布为1组人类致癌物。有充分证据表明，在包括中国在内的亚洲特大城市，接触率非常高。我们在长江流域地区（启东）的研究揭示了一系列空气中有毒物质的高内剂量水平，这可能反映了经济发展的激增，而没有同时注意区域环境保护。减少接触空气中的有毒物质需要在国家和全球任务的推动下进行大量的经济和政治投资，而这些任务已证明难以执行。然而，化学预防，特别是基于食物的“绿色”化学预防，为个人减轻与这些不可避免的接触有关的风险提供了机会。基于我们以前的临床试验表明，西兰花芽提取物（富含化学预防剂萝卜硫素及其前体萝卜硫苷）增强了环境暴露中多种空气传播毒物的解毒作用，我们将研究一种新的膳食补充剂，该膳食补充剂使用巧妙，廉价的配方在体内提供一致的，生物可利用的萝卜硫素来源。我们的假设是，这些危险生物标志物水平的调节程度（例如，挥发性巯基尿酸 有机空气污染物）的影响可以预测化学预防干预措施在高危人群中的效果，并将指导其优化和转化为实践。该项目的具体目标是详细了解过去和新出现的暴露于空气中有毒物质的模式。为了实现这一目标，我们将使用我们早期在中国启东进行的研究中20年的纵向样本来量化空气有毒物质水平的变化程度。这些模式将在启东市非吸烟女性肺癌风险最近迅速增加的背景下进行评估。我们还将优化剂量和时间表的机制为基础的化学预防干预与西兰花衍生的膳食补充剂，以加强解毒这些化学空气传播的危害。我们寻求提供节俭的方法，以减轻环境毒素的行动，立法或监管办法是不可行的，目前。

 DESCRIPTION (provided by applicant): Air pollution has recently been declared a Group 1 human carcinogen by IARC. It is well documented that exposures are very high in Asian megacities including those in China. Our studies in the Yangtze River Basin region (Qidong) have revealed high internal dose levels of a spectrum of airborne toxicants, presumably reflecting the surge in economic development without concomitant attention to regional environmental protection. Reductions in exposures to airborne toxicants require substantive economic and political investments, driven by national and global mandates, which have proven difficult to implement. However, chemoprevention, especially food-based "green" chemoprevention, offers the opportunity for individuals to mitigate risks associated with these unavoidable exposures. Based upon our previous clinical trials demonstrating that broccoli sprout extracts (rich in the chemopreventive agent sulforaphane and its precursor glucoraphanin) enhanced the detoxication of multiple airborne toxicants from ambient exposures, we will examine a new dietary supplement that provides a consistent, bioavailable source of sulforaphane in the body using a clever, inexpensive formulation. It is our hypothesis that the extent of modulation of these hazard biomarker levels (e.g., mercapturic acids of volatile organic air pollutants) can predict the efficacy of chemopreventive interventions in at-risk populations and will guide their optimization and translation to practice. The specific aims of thi project are designed to understand, in detail, past and emerging patterns of exposure to airborne toxicants. To achieve the aims, we will use longitudinal samples over a 20- year period from our earlier studies in Qidong, China to quantify the extent of changes occurring in levels of air toxicants. These patterns will be evaluated in the context of recent, rapidly increasing risk o lung cancer in non-smoking women in Qidong. We will also optimize dose and schedule for a mechanism-based chemoprevention intervention with a broccoli-derived dietary supplement for enhanced detoxication of these chemical airborne hazards. We seek to provide frugal approaches to mitigate the actions of environmental toxins where legislative or regulatory approaches are not feasible at present.