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Benzo(a)pyrene induces similar gene expression changes in testis of DNA repair proficient and deficient male mice

ABSTRACT: DNA damage induced by benzo(a)pyrene may lead to the formation of mutations and as a consequence to the development of diseases. However, it is uncertain whether benzo(a)pyrene causes heritable mutations in male germ cells, which would increase health risks in offspring. In a previous study, benzo(a)pyrene induced DNA damage was observed at all stages of spermatogenesis and in testis. In addition, we observed that spermatogonial stem cells and testis rely, at least in part, on nucleotide excision repair for the removal of this damage, because removal was less efficient in Xpc-/- than in wild type mice. Efficient removal will protect the germ cells against the formation of heritable mutations. By using microarray technology, we investigated in this study the consequences of this difference in DNA adduct removal at the level of gene expression in testis 4 days after a single exposure to benzo(a)pyrene.

ORGANISM(S): Mus musculus

PROVIDER: GSE17979 | GEO | 2010/08/24

SECONDARY ACCESSION(S): PRJNA120011

REPOSITORIES: GEO

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Benzo(a)pyrene induces similar gene expression changes in testis of DNA repair proficient and deficient male mice

Project description:DNA damage induced by benzo(a)pyrene may lead to the formation of mutations and as a consequence to the development of diseases. However, it is uncertain whether benzo(a)pyrene causes heritable mutations in male germ cells, which would increase health risks in offspring. In a previous study, benzo(a)pyrene induced DNA damage was observed at all stages of spermatogenesis and in testis. In addition, we observed that spermatogonial stem cells and testis rely, at least in part, on nucleotide excision repair for the removal of this damage, because removal was less efficient in Xpc-/- than in wild type mice. Efficient removal will protect the germ cells against the formation of heritable mutations. By using microarray technology, we investigated in this study the consequences of this difference in DNA adduct removal at the level of gene expression in testis 4 days after a single exposure to benzo(a)pyrene. We analyzed 20 testis samples of mice divided into 4 groups (5 mice per group): C57BL/6 control mice, C57BL/6 mice exposed to B[a}P, Xpc-/- control mice, Xpc-/- mice exposed to B[a]P. We used a pool of 3 C57BL/6 control mice as a reference.

2010-08-23 | E-GEOD-17979 | biostudies-arrayexpress

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Acute hepatic transcriptional response in male mice following oral exposure to benzo(a)pyrene

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: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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benzo(a)pyrene_MCF7_HepG2

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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

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

2020-05-26 | PXD010610 | Pride

Quantification and mapping of alkylation in the human genome reveal single nucleotide resolution precursors of mutational signatures

Project description:Benzo[a]pyrene (BaP) is a known human carcinogen (IARC Group 1) found in food, coal tar, as well as cigarettes and other smoke. Its diol-epoxide metabolites (Benzo[a]pyrene diol-epoxide [BPDE]) react with DNA forming DNA adducts, predominantly N2-BPDE-deoxyguanosine (N2-BPDE-dG). While the capacity of BPDEs to alkylate DNA and induce mutations is well known, little is known about how the genomic features influence the accumulation of DNA damage at a genome-wide level. To bridge this gap, we developed a single-nucleotide resolution damage sequencing method to map N2-BPDE-dG in a BPDE exposed human lung cell line, and combined this analysis with mass spectrometry to quantify the total absolute levels of the adduct in the genome. Comparing damage abundance with DNase hypersensitive sites, transcription levels, and other genome annotation data showed that although the overall adduct levels increased with increasing concentration of BPDE, the genomic distribution patterns of N2-BPDE-dG were stable and correlated with the genomic features related to chromatin state and transcriptional activities. In addition, we extracted the preferred local DNA sequence contexts for N2-BPDE-dG, i.e., its DNA damage signature, and found that it was highly similar to the mutational signatures identified from smoking-related lung cancers. These results suggest that genomic features and sequence contexts are important in shaping the landscape of DNA damage arising from chemical exposures and provide an effective strategy for linking single-nucleotide resolution damage sequencing data with cancer mutations.

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