|Grant Number:||5R21CA094715-03 Interpret this number|
|Primary Investigator:||Christiani, David|
|Organization:||Harvard University (Sch Of Public Hlth)|
|Project Title:||Biomarkers of Carcinogen Exposure and Oxidative Injury|
Cancer remains the second leading cause of death m the US preceded only by heart disease. The great majority of cancers are believed to be preventable because of known environmental factors that influence their incidence. Air pollution, predominantly composed of particulates including polycyclic aromatic hydrocarbons (PAH) and metals is known to contain significant levels of reactive oxygen species (ROS) which can lead to deleterious effects within a normal cell. Continued, repeated exposure to ROS (as seen in occupational exposures) leads to oxidative injury within a cell that can directly affect DNA, cell signaling and growth and the induction of mitosis and initiate the multi- step cascade of carcinogenesis. Previous epidemiologic studies have demonstrated increased cancer incidence among workers exposed to particulates and PAR The proposed investigation will use a repeated measures, short-term prospective approach to study exposure to particulates, PAH and metals and their relationship to oxidative injury biomarkers as intermediate factors in the development of cancer in a cohort of occupationally exposed individuals. This study will address important gaps in current knowledge of epidemiologic exposure assessment and will provide the opportunity to characterize both biologic markers of exposure (1-hydroxypyrene, mononuclear PAH- DNA adducts, urinary metals and urinary 7,8-dihydro-2'- deoxyguanosine;8-OH-dG), and biomarkers of early environmental carcinogen damage (PAH-DNA adducts, urinary 8-OH-dG). This study specifically addresses several of the key areas detailed in the RFA, including characterization and quantification of exposures and exposed populations via evaluation of the suitability of the use of several biomarkers simultaneously collected in surrogate tissue (blood DNA adducts, urinary metals, urinary 8-OH-dG and urinary 1- hydroxypyrene). A better understanding of these risks will lead to improved preventive strategies.