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Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells

Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action...

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Autores principales: Barhoumi, Rola, Mouneimne, Youssef, Chapkin, Robert S., Burghardt, Robert C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961214/
https://www.ncbi.nlm.nih.gov/pubmed/24651647
http://dx.doi.org/10.1371/journal.pone.0090908
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author Barhoumi, Rola
Mouneimne, Youssef
Chapkin, Robert S.
Burghardt, Robert C.
author_facet Barhoumi, Rola
Mouneimne, Youssef
Chapkin, Robert S.
Burghardt, Robert C.
author_sort Barhoumi, Rola
collection PubMed
description Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action. In this investigation, the effects of control fatty acids (oleic acid (OA), linoleic acid (LA)) and n-3 PUFA, e.g., docosahexaenoic acid (DHA) on the uptake and metabolism of the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) was investigated in A549 cells, a human adenocarcinoma alveolar basal epithelial cell line. A549 cells activate BaP through the cytochrome P450 enzyme system to form reactive metabolites, a few of which covalently bind to DNA and proteins. Therefore, multiphoton microscopy spectral analysis combined with linear unmixing was used to identify the parent compound and BaP metabolites formed in cells, in the presence and absence of fatty acids. The relative abundance of select metabolites was associated with altered P450 activity as determined using ethoxyresorufin-O-deethylase activity in cells cultured in the presence of BSA-conjugated fatty acids. In addition, the parent compound within cellular membranes increases significantly in the presence of each of the fatty acids, with the greatest accumulation observed following DHA treatment. DHA treated cells exhibit significantly lower pyrene-like metabolites indicative of lower adducts including DNA adducts compared to control BSA, OA or LA treated cells. Further, DHA reduced the abundance of the proximate carcinogen BaP 7,8-dihydrodiol and the 3-hydroxybenzo[a]pyene metabolites compared to other treatments. The significant changes in BaP metabolites in DHA treated cells may be mediated by the effects on the physicochemical properties of the membrane known to affect enzyme activity related to phase I and phase II metabolism. In summary, DHA is a highly bioactive chemo-protective agent capable of modulating BaP-induced DNA adducts.
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spelling pubmed-39612142014-03-24 Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells Barhoumi, Rola Mouneimne, Youssef Chapkin, Robert S. Burghardt, Robert C. PLoS One Research Article Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action. In this investigation, the effects of control fatty acids (oleic acid (OA), linoleic acid (LA)) and n-3 PUFA, e.g., docosahexaenoic acid (DHA) on the uptake and metabolism of the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) was investigated in A549 cells, a human adenocarcinoma alveolar basal epithelial cell line. A549 cells activate BaP through the cytochrome P450 enzyme system to form reactive metabolites, a few of which covalently bind to DNA and proteins. Therefore, multiphoton microscopy spectral analysis combined with linear unmixing was used to identify the parent compound and BaP metabolites formed in cells, in the presence and absence of fatty acids. The relative abundance of select metabolites was associated with altered P450 activity as determined using ethoxyresorufin-O-deethylase activity in cells cultured in the presence of BSA-conjugated fatty acids. In addition, the parent compound within cellular membranes increases significantly in the presence of each of the fatty acids, with the greatest accumulation observed following DHA treatment. DHA treated cells exhibit significantly lower pyrene-like metabolites indicative of lower adducts including DNA adducts compared to control BSA, OA or LA treated cells. Further, DHA reduced the abundance of the proximate carcinogen BaP 7,8-dihydrodiol and the 3-hydroxybenzo[a]pyene metabolites compared to other treatments. The significant changes in BaP metabolites in DHA treated cells may be mediated by the effects on the physicochemical properties of the membrane known to affect enzyme activity related to phase I and phase II metabolism. In summary, DHA is a highly bioactive chemo-protective agent capable of modulating BaP-induced DNA adducts. Public Library of Science 2014-03-20 /pmc/articles/PMC3961214/ /pubmed/24651647 http://dx.doi.org/10.1371/journal.pone.0090908 Text en © 2014 Barhoumi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Barhoumi, Rola
Mouneimne, Youssef
Chapkin, Robert S.
Burghardt, Robert C.
Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells
title Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells
title_full Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells
title_fullStr Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells
title_full_unstemmed Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells
title_short Effects of Fatty Acids on Benzo[a]pyrene Uptake and Metabolism in Human Lung Adenocarcinoma A549 Cells
title_sort effects of fatty acids on benzo[a]pyrene uptake and metabolism in human lung adenocarcinoma a549 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961214/
https://www.ncbi.nlm.nih.gov/pubmed/24651647
http://dx.doi.org/10.1371/journal.pone.0090908
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