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

Authors

Language

English

Publication Date

9-1-2024

Journal

Chemosphere

DOI

10.1016/j.chemosphere.2024.143121

PMID

39154768

PMCID

PMC11424241

PubMedCentral® Posted Date

9-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Benzo(a)pyrene, Humans, Cytochrome P-450 CYP1B1, Signal Transduction, Transcriptome, Receptors, Aryl Hydrocarbon, ASB2, Benzo[a]pyrene, CYP1B1, gene expression, meta-analysis

Published Open-Access

yes

Recommended Citation

, "Meta-Analysis Identifies Key Genes and Pathways Implicated in Benzo[a]pyrene Exposure Response" (2024). Faculty, Staff and Student Publications. 1254.
https://digitalcommons.library.tmc.edu/uthsph_docs/1254