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Grant Details

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
Fiscal Year: 2003
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Abstract

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.

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Publications

pH increase observed in exhaled breath condensate from welding fume exposure.
Authors: Boyce PD, Kim JY, Weissman DN, Hunt J, Christiani DC
Source: J Occup Environ Med, 2006 Apr;48(4), p. 353-6.
PMID: 16607188
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A urinary metabolite of phenanthrene as a biomarker of polycyclic aromatic hydrocarbon metabolic activation in workers exposed to residual oil fly ash.
Authors: Kim JY, Hecht SS, Mukherjee S, Carmella SG, Rodrigues EG, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2005 Mar;14(3), p. 687-92.
PMID: 15767350
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Exposure to welding fumes is associated with acute systemic inflammatory responses.
Authors: Kim JY, Chen JC, Boyce PD, Christiani DC
Source: Occup Environ Med, 2005 Mar;62(3), p. 157-63.
PMID: 15723880
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Urinary 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates.
Authors: Kim JY, Mukherjee S, Ngo LC, Christiani DC
Source: Environ Health Perspect, 2004 May;112(6), p. 666-71.
PMID: 15121508
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Smoking status and occupational exposure affects oxidative DNA injury in boilermakers exposed to metal fume and residual oil fly ash.
Authors: Mukherjee S, Palmer LJ, Kim JY, Aeschliman DB, Houk RS, Woodin MA, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2004 Mar;13(3), p. 454-60.
PMID: 15006923
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