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.

PUBLIC HEALTH RELEVANCE: Critical environmental exposures contribute to chronic disease across the life span, especially in economically developing regions of the world. Using archived and prospective urine samples, we will measure changing exposures to airborne pollutants in Qidong, China and evaluate associations to recent, rapidly increasing lung cancer rates in that region in non-smoking women. While reductions in exposures will require substantive economic and political investments, chemoprevention trials, especially the food-based "green" chemoprevention that we propose with a novel dietary supplement, offer opportunities for individuals to mitigate risks associated with these unavoidable exposures.