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Cumulative metabolic effects of low-dose benzo(a)pyrene exposure on human cells.

ABSTRACT: Benzo(a)pyrene (B[a]P) is a common environmental and foodborne pollutant which has been identified as a Group I carcinogen. Although the carcinogenicity of B[a]P has been illustrated, its comprehensive influence on metabolism and further relevance in adverse health outcomes are not well understood. To investigate the global metabolic effects of long-term B[a]P exposure at environmental dosage, we utilized the human SMMC-7721 cell-based B[a]P exposure models to perform a metabolomics study and network analysis. A total of 316 biochemicals were identified and 104 metabolites were found to be significantly altered. Bioinformatics analysis showed that the amino acid, carbohydrate, and lipid metabolism pathways and the nucleotide metabolism pathway were influenced by prolonged B[a]P exposure. Notably, the metabolic effects of B[a]P varied with different dosages. In addition, B[a]P exposure caused a decline in the glycolysis process but enhanced the glycolytic capability of SMMC-7721 cells in vitro. These findings establish the overall B[a]P-induced metabolic network, characterize the metabolic effects of chronic and environmental B[a]P exposure on human-relevant cells, and enhance the understanding of the adverse outcome pathway frame of B[a]P.

SUBMITTER: Ba Q

PROVIDER: S-EPMC6062128 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Cumulative metabolic effects of low-dose benzo(a)pyrene exposure on human cells.

Ba Qian Q Huang Chao C Fu Yijing Y Li Junyang J Li Jingquan J Chu Ruiai R Jia Xudong X Wang Hui H

Toxicology research 20151118 1

Benzo(a)pyrene (B[a]P) is a common environmental and foodborne pollutant which has been identified as a Group I carcinogen. Although the carcinogenicity of B[a]P has been illustrated, its comprehensive influence on metabolism and further relevance in adverse health outcomes are not well understood. To investigate the global metabolic effects of long-term B[a]P exposure at environmental dosage, we utilized the human SMMC-7721 cell-based B[a]P exposure models to ...[more]

PMID: 30090330

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Project 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]pyrene 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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Cumulative metabolic effects of low-dose benzo(a)pyrene exposure on human cells.

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Cumulative metabolic effects of low-dose benzo(<i>a</i>)pyrene exposure on human cells.

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