Meta-analysis identifies key genes and pathways implicated in Benzo[a]pyrene exposure response.
Chemosphere
; 364: 143121, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39154768
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 expressionanalysis:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Benzo(a)pireno
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Transdução de Sinais
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Citocromo P-450 CYP1B1
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article