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Benzo[a]pyrene and dibenzo[def,p]chrysene in 3D primary human bronchial epithelial cells [miRNA-seq]

ABSTRACT: Benzo[a]pyrene and dibenzo[def,p]chrysene in 3D primary human bronchial epithelial cells [miRNA-seq]

PROVIDER: PRJNA527841 | ENA |

REPOSITORIES: ENA

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Benzo[a]pyrene and dibenzo[def,p]chrysene in 3D primary human bronchial epithelial cells [miRNA-seq]

Project description:In this study, we assess potential differences in mechanism of action for two PAHs, benzo[a]pyrene (BAP) and dibenzo-[def,p]chrysene (DBC), in a primary human 3D bronchial epithelial culture (HBEC) model based on short-term biosignatures identified from global transcriptional profiling.

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Benzo[a]pyrene and dibenzo[def,p]chrysene in 3D primary human bronchial epithelial cells [RNA-seq]

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Benzo[a]pyrene and dibenzo[def,p]chrysene in 3D primary human bronchial epithelial cells [RNA-seq]

Project description:Benzo[a]pyrene and dibenzo[def,p]chrysene in 3D primary human bronchial epithelial cells [RNA-seq]

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Cytochrome P450 Monooxygenase Mediated Metabolic Utilization of Benzo(a)pyrene by Fungi

Project description:Soil dwelling Aspergillus fungi possess the versatile metabolic capability to utilize complex organic compounds which are toxic to humans, yet the mechanisms they employ remain largely unknown. Benzo(a)pyrene is a common carcinogenic contaminant, posing a significant concern for human health. Here, we report that Aspergillus fungi can degrade benzo(a)pyrene effectively. In Aspergillus nidulans, exposure to benzo(a)pyrene results in transcriptomic and metabolic changes associated with cellular growth and energy generation, implying that the fungus utilizes benzo(a)pyrene as a food. Importantly, we identify and characterize the conserved bapA gene encoding a cytochrome P450 monooxygenase that exerts the first step in the degradation of benzo(a)pyrene. We further demonstrate that the fungal NF-κB-type global regulators VeA and VelB are required for benzo(a)pyrene degradation in A. nidulans, which occurs through expression control of bapA in response to nutrient limitation. Our study illuminates fundamental knowledge of fungal benzo(a)pyrene metabolism and provides novel insights into enhancing bioremediation potential.

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Project description:Benzo(a)pyrene is a well-established human carcinogen in humans and rodents. In the present study, we sought to determine the dose- and time-dependent changes in gene expression upon oral exposure to benzo(a)pyrene. Adult male B6C3F1 mice were exposed to four doses of benzo(a)pyrene or vehicle control for three days and sacrificed 4 or 24 hours after the final exposure.

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Project description:The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1 ) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response of mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by 32P post- labeling, did not correlate with tumor incidence. PAH dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p<0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs).

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Transcriptomic response to benzo[a]pyrene treatment in HepG2 cells

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