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Combustion-Derived Hydrocarbons Localize to Lipid Droplets in Respiratory Cells

¹ Comparative Biomedical Sciences, School of Veterinary Medicine; ² Division of Biotechnology & Molecular Medicine (BioMMED), School of Veterinary Medicine; and ³ Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana

Correspondence and requests for reprints should be addressed to Dr. Arthur Penn, Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803. E-mail: apenn{at}vetmed.lsu.edu

Combustion-generated radicals interact to form polynuclear aromatic hydrocarbons (PAHs), including carcinogens. PAHs aggregate into 20- to 50-nm particles, which extend into branched-chain structures (soots). Incomplete combustion yields black soot particles and black smoke. Many PAHs, including those in soots, fluoresce upon excitation. We have reported that butadiene soot (BDS), generated during combustion of the high-volume petrochemical 1,3-butadiene, serves as a reproducible example of combustion-derived fine and ultrafine particles, with the potential for acute or delayed health effects. Human bronchoepithelial cells (BEAS-2B) display time- and concentration-dependent responses to BDS exposure, culminating in concentration of fluorescent PAHs within discrete cytoplasmic bodies. Here we identify the cytoplasmic compartment(s) in which combustion-derived PAHs concentrate and assess the metabolic responses associated with this compartmentalization. BDS-associated fluorescence colocalized with a red fluorescent cholesterol analog and a transfected plasmid coding for a fluorescent lipid droplet surface protein within BEAS-2B cells. After BDS exposure, murine alveolar macrophages (MH-S) and adipocytes (3T3-L1) also develop fluorescence. These findings, especially within adipocytes, support the accumulation of PAHs within lipid droplets. Microarray data revealed up-regulation of aryl hydrocarbon receptor–induced Phase I biotransformation enzymes and nuclear erythroid-2 related factor 2–mediated oxidative stress responses in BEAS-2B cells. Quantitative RT-PCR results confirmed a time-dependent up-regulation of Phase I biotransformation enzymes (CYP1A1, CYP1B1, and ALDH3A1) in BDS-exposed BEAS-2B and MH-S cells. Thus, respiratory cell lipid droplets concentrate PAHs delivered by combustion-derived ultrafine particles. These PAHs, including several found in BDS and in cigarette smoke, activate xenobiotic metabolism pathways and thereby potentiate their toxicity.

Key Words: lipid droplets • fluorescence • soot • polynuclear aromatic hydrocarbons • xenobiotic metabolism

CLINICAL RELEVANCE Hydrocarbons, including carcinogens, on inhalable petrochemical combustion particles and present in cigarette smoke, localize to lipid droplets in respiratory cells and adipocytes. Lipid droplets may serve in storage/release of environmental toxicants.