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Modulating the Response to Benzo[a]pyrene when CYP1A1 and CYP1B1 are Knocked Down

ABSTRACT: Modulating the Response to Benzo[a]pyrene when CYP1A1 and CYP1B1 are Knocked Down

PROVIDER: PRJNA1060252 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27404339.fastq.gz	Fastqsanger.gz
	SRR27404340.fastq.gz	Fastqsanger.gz
	SRR27404341.fastq.gz	Fastqsanger.gz

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Modulating the Response to Benzo[a]pyrene when CYP1A1 and CYP1B1 are Knocked Down

Project description:Benzo[a]pyrene is a Group 1 carcinogen. It undergoes metabolism in the liver through CYP1A1 and CYP1B1 enzymes. This study was conducted to investigate the response to benzo[a]pyrene in the liver when these enzymes are knocked down.

2024-01-03 | GSE252339 | GEO

Cyp1b1-mediated suppression of lymphoid progenitors in bone marrow coordinately impacts spleen and thymus

Project description:C57BL/6j mice were treated with polycyclic aromatic hydrocarbons (benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, and 2,3,7,8 tetrachlorodibenzo-p-dioxin) Cyp1a1 and Cyp1b1 deletion separately and in combination were evaluated relative to the intact WT mice

2016-06-06 | GSE82242 | GEO

Oral Benzo[a]pyrene in Cyp1a1/1b1(-/-) Double-Knockout Mice: Microarray Analysis During Squamous Cell Carcinoma Formation in Preputial Gland Duct

Project description:Benzo[a]pyrene (BaP) is a prototypical polycyclic aromatic hydrocarbon (PAH) found in combustion processes. Cytochrome P450 1A1 and 1B1 enzymes (CYP1A1, CYP1B1) and other enzymes can activate PAHs to reactive oxygenated intermediates involved in mutagenesis and tumor initiation; also, CYP1 enzymes can detoxify PAHs. Cyp1(+/+) wild-type (WT) and Cyp1b1(-/-) knockout mice receiving oral BaP (12.5 mg/kg/day) remain healthy for >12 months. In contrast, we found that global knockout of the Cyp1a1 gene (1a1KO) results in proximal small intestine (PSI) adenocarcinoma within 8 to 12 weeks on this BaP regimen; striking compensatory increases in PSI CYP1B1 likely participate in initiation of adenocarcinoma in 1a1KO mice. Cyp1a1/1b1(-/-) double-knockout (DKO) mice on this BaP regimen show no PSI adenocarcinoma, but instead preputial gland duct (PGD) squamous cell carcinoma (SCC) occurs by 12 weeks. Herein we compare microarray expression of PGD genes in WT, 1a1KO and DKO mice at zero, 4, 8, 12, and 16 weeks of oral BaP; about four dozen genes up- or down-regulated during the most critical time-points were further verified by qRT-PCR. In DKO mice, CYP3A59 was unequivocally identified as the BaP-inducible and BaP-metabolizing best candidate responsible for initiation of BaP-induced SCC. Striking increases or decreases were found in 26 cancer-related genes plus eight Serpin genes in DKO, but not in 1a1KO or WT, mice on this BaP regimen; of the 26, eight were RAS-related oncogenes. The mechanism by which cancer-related genes are responsible for SCC tumor progression in the PGD remains to be elucidated. The tissue being tested is preputial gland duct of mice. Three genotypes (WT, Cyp1a1 KO and Cyp1a1/1b1 DKO) were compared with one another, at zero, 4, 8, 12 and 16 weeks of oral BaP. The five time-points within each genotype were also compared.

2012-09-06 | E-GEOD-40633 | biostudies-arrayexpress

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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Glutathione S-transferase induction after exposure to benzo[a]pyrene

Project description:Benzo[a]pyrene induction of glutathione S-transferases, an activity-based protein profiling investigation

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Oral Benzo[a]pyrene in Cyp1a1/1b1(-/-) Double-Knockout Mice: Microarray Analysis During Squamous Cell Carcinoma Formation in Preputial Gland Duct

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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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Defining the transcriptomic fingerprints of benzo[a]pyrene exposure in Caenorhabditis elegans

Project description:Polycyclic aromatic hydrocarbons (PAHs) are abundant organic compounds and are anthropogenically produced by the incomplete combustion of organic matter (e.g. fossil fuels and tobacco smoke). One notable model PAH is benzo[a]pyrene (BaP), which is listed as a Group 1 human carcinogen by the International Agency of Research on Cancer (IARC). Although the mode of action for BaP is well known in higher organisms, limited knowledge is available regarding the consequence of BaP exposure in the model organism Caenorhabditis elegans. The objective of this study was to define the the global transcriptome of wild-type C. elegans exposed to BaP (0, 5 and 20 μM). The most responsive transcripts were linked to redox processes and xenobiotic responses, including P450 enzymes (CYPs) (mainly members of the CYP35 family), epoxide hydrolases (EHs), glutathione S-transferases (GSTs), and UDP-glucuronosyltransferases (UGTs), all of which are linked to the metabolism (phase I & II) of xenobiotic substances. In summary, although the dominant CYP1A1/2 & CYP1B1 metabolic pathway is absent in C. elegans, BaP still induced a strong transcriptomic response. This provides strong evidence that parallel pathway(s) are implicated in BaP metabolism, and possibly, in its detoxification.

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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 MutaTMMouse were exposed to three doses of benzo(a)pyrene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.

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Effect of the genotoxic human lung carcinogen benzo[a]pyrene and its non-carcinogenic isomer benzo[e]pyrene on transcriptomic profiles in HepaRG cells.

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