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Your Environment. Your Health.

Final Progress Reports: Louisiana State University: Pollutant-Particle Systems and Xenobiotic Bioactivation (ARRA Funded)

Superfund Research Program

Pollutant-Particle Systems and Xenobiotic Bioactivation (ARRA Funded)

Project Leader: Wayne L. Backes (LSU Health Sciences Center - New Orleans)
Grant Number: P42ES013648
Funding Period: 2009-2011

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Final Progress Reports

Year:   2010 

Combustion products consist of significant amounts of fine and ultrafine particles that are capable of penetrating deep into the lung and accessing the systemic circulation, causing cardiac toxicity, pulmonary toxicity, and genotoxicity. The pollutant/particle systems have been implicated as potential health hazards, through the generation of reactive oxygen species (ROS). The goal of this project is to examine the role of cytochrome P450 in the bioactivation of particulate matter, and to identify the components of particulates responsible for its modulation. Specifically, research is being conducted to determine whether ultrafine particles and their associated environmentally persistent free radicals (EPFR)-generating components not only influence cytochrome P450-dependent metabolism, but also alter their expression and activity.

Dr. Backes’ research group has begun to examine the ability of ultra-fine particle components to modulate P450 expression in the lungs from normal rats and to examine the potential for reactive oxygen species generation by the P450 system and the effect of particle exposure on ROS production. They have also included preliminary studies that touch on the mechanism of the changes in P450 expression and toxicity: to investigate the role of the NFκB signaling pathway, which has been implicated as a general response to oxidative stress in the cellular response to EPFR exposure.

By understanding the involvement of NFκB signaling in the response to EPFR exposure, the researchers can elucidate the source of the biological response which may lead to therapeutic remedies related to EPFR toxicity. They have also optimized and tested a repeated, inhalational dosing regimen under conditions which are more comparable to those expected following exposure of humans to EPFRs from Superfund waste sites.

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