Meta-analysis Identifies Key Genes and Pathways Implicated in Benzo[a]pyrene Exposure Response

Details

• Alternative Title:
  Chemosphere
• Personal Author:
  Zhu, Mingze ; Hwang, Jooyeon ; Xu, Chao
• Description:
  Introduction: ; Benzoapyrene (BaP) is a carcinogenic polycyclic aromatic hydrocarbon that poses significant risks to human health. BaP influences cellular processes via intricate interactions; however, a comprehensive understanding of BaP’s effects on the transcriptome remains elusive. This study aimed to conduct a comprehensive analysis focused on identifying relevant genes and signaling pathways affected by BaP exposure and their impact on human gene expression. ; Methods: ; We searched the Gene Expression Omnibus database and identified four studies involving BaP exposure in human cells (T lymphocytes, hepatocellular carcinoma cells, and C3A cells). We utilized two approaches for differential expression analysis: the LIMMA package and linear regression. A meta-analysis was utilized to combine log fold changes (FC) and p-values from the identified studies using a random effects model. We identified significant genes at a Bonferroni-adjusted significance level of 0.05 and determined overlapping genes across datasets. Pathway enrichment analysis elucidated key cellular processes modulated by BaP exposure. ; Results: ; The meta-analysis revealed significant upregulation of CYP1B1 (log FC = 1.15, 95% CI: 0.51-1.79, P < 0.05, I2 = 82%) and ASB2 (log FC = 0.44, 95% CI: 0.20-0.67, P < 0.05, I2 = 40%) in response to BaP exposure. Pathway analyses identified 26 significantly regulated pathways, with the top including Aryl Hydrocarbon Receptor Signaling (P = 0.00214) and Xenobiotic Metabolism Signaling (P = 0.00550). Key genes CYP1A1, CYP1B1, and CDKN1A were implicated in multiple pathways, highlighting their roles in xenobiotic metabolism, oxidative stress response, and cell cycle regulation. ; Conclusion: ; The results provided insights into the mechanisms of BaP toxicity, highlighting CYP1B1’s key role in BaP bioactivation. The findings underscored the complexity of BaP’s mechanisms of action and their potential implications for human health. The identified genes and pathways provided a foundation for further exploration and enhanced our understanding of the multifaceted biological activities associated with BaP exposure.
• Subjects:
  • Benzo(a)pyrene
  • Humans
  • Cytochrome P-450 CYP1B1
  • Signal Transduction
  • Transcriptome
  • Receptors, Aryl Hydrocarbon
• Keywords:
  • ASB2
  • Benzoapyrene
  • CYP1B1
  • gene expression
  • meta-analysis
• Source:
  Chemosphere. 364:143121
• Pubmed ID:
  39154768
• Pubmed Central ID:
  PMC11424241
• Document Type:
  Journal Article
• Funding:
  K01 OH011891/OH/NIOSH CDC HHSUnited States/ ; T42 OH008421/OH/NIOSH CDC HHSUnited States/ ; U19 AG055373/AG/NIA NIH HHSUnited States/
• Volume:
  364
• Download URL:
  https://stacks.cdc.gov/view/cdc/164024/cdc_164024_DS1.pdf
• File Type:
  [PDF - 838.91 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:2b09ef5ef9f33c678cc0f3671d3c693c3c6c39b85f8edd7776a932dfa40e2ae13fbca083b6dc4ac25ff336dab1766b11eab56fa7f3cbd0564924fa933e492142