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

Details

• Personal Author:
  Hwang J ; Xu C ; Zhu M
• Description:
  Introduction: Benzo[a]pyrene (B[a]P) is a carcinogenic polycyclic aromatic hydrocarbon that poses significant risks to human health. B[a]P influences cellular processes via intricate interactions; however, a comprehensive understanding of B[a]P'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 B[a]P exposure and their impact on human gene expression. Methods: We searched the Gene Expression Omnibus database and identified four studies involving B[a]P 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 B[a]P 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 B[a]P 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 B[a]P toxicity, highlighting CYP1B1's key role in B[a]P bioactivation. The findings underscored the complexity of B[a]P'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 B[a]P exposure. [Description provided by NIOSH]
• Subjects:
  Hydrocarbons Occupational Health Polycyclic Aromatic Hydrocarbons Safety
• Keywords:
  Author Keywords: ASB2 B(a)P Benzo(a)pyrene Benzo[a]pyrene Bioactivation CYP1B1 Gene Expression Meta-analysis Oxidative Stress Polycyclic Aromatic Hydrocarbons Toxic Effects

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• ISSN:
  0045-6535
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Oklahoma ; OSHA Region 6 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  364
• NIOSHTIC Number:
  nn:20070093
• Citation:
  Chemosphere 2024 Sep; 364:143121
• Contact Point Address:
  Jooyeon Hwang, Department of Environmental & Occupational Health Sciences, School of Public Health, University of Texas Health Science Center, Houston, TX, 77030, USA
• Email:
  jooyeon.hwang@uth.tmc.edu
• CAS Registry Number:
  Benzo[a]pyrene (CAS RN 50-32-8)
• Federal Fiscal Year:
  2024
• Performing Organization:
  University of Oklahoma Health Sciences Center, Oklahoma City
• Peer Reviewed:
  True
• Start Date:
  20200901
• Source Full Name:
  Chemosphere
• End Date:
  20210831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:34e78ba4e135e439891bfa725839c3ceda24d220ffe68c74783d1b1dc677b72463903a01ea055104a95cd1e8c82503febf77bdb53067c0cabb31a534c1853f44
• Download URL:
  https://stacks.cdc.gov/view/cdc/208386/cdc_208386_DS1.pdf
• File Type:
  [PDF - 2.59 MB ]