Department of Occupational and Environmental Health, Hudson College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, OK, 73104, USA.
Department of Occupational and Environmental Health, Hudson College of Public Health, University of Oklahoma Health Sciences, Oklahoma City, OK, 73104, USA; Department of Environmental & Occupational Health Sciences, School of Public Health, University of Texas Health Science Center, Houston, TX, 77030, USA; Southwest Center for Occupational and Environmental Health, University of Texas Health Science Center, Houston, TX, 77030, USA.
Chemosphere. 2024 Sep;364:143121. doi: 10.1016/j.chemosphere.2024.143121. Epub 2024 Aug 21.
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.
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.
The meta-analysis revealed significant upregulation of CYP1B1 (log FC = 1.15, 95% CI: 0.51-1.79, P < 0.05, I = 82%) and ASB2 (log FC = 0.44, 95% CI: 0.20-0.67, P < 0.05, I = 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.
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.
苯并[a]芘（B[a]P）是一种致癌的多环芳烃，对人类健康构成重大威胁。B[a]P 通过复杂的相互作用影响细胞过程；然而，对 B[a]P 对转录组影响的全面理解仍然难以捉摸。本研究旨在进行全面分析，重点识别受 B[a]P 暴露影响的相关基因和信号通路及其对人类基因表达的影响。
我们在基因表达综合数据库中进行了检索，确定了四项涉及人类细胞（T 淋巴细胞、肝癌细胞和 C3A 细胞）中 B[a]P 暴露的研究。我们使用两种差异表达分析方法：LIMMA 包和线性回归。使用随机效应模型对从已确定研究中识别出的 log 倍数变化（FC）和 p 值进行荟萃分析。我们确定了在 Bonferroni 调整的显著性水平为 0.05 时有意义的基因，并确定了数据集之间的重叠基因。通路富集分析阐明了 B[a]P 暴露调节的关键细胞过程。
荟萃分析显示，CYP1B1（log FC=1.15，95%CI：0.51-1.79，P<0.05，I=82%）和 ASB2（log FC=0.44，95%CI：0.20-0.67，P<0.05，I=40%）的显著上调。对 B[a]P 暴露有反应。通路分析确定了 26 个受显著调节的通路，其中包括芳香烃受体信号（P=0.00214）和外源代谢信号（P=0.00550）。关键基因 CYP1A1、CYP1B1 和 CDKN1A 参与了多个通路，突出了它们在外源代谢物生物激活、氧化应激反应和细胞周期调节中的作用。
结果提供了对 B[a]P 毒性机制的深入了解，突出了 CYP1B1 在 B[a]P 生物激活中的关键作用。研究结果强调了 B[a]P 作用机制的复杂性及其对人类健康的潜在影响。鉴定的基因和途径为进一步探索提供了基础，并增强了我们对与 B[a]P 暴露相关的多方面生物学活性的理解。
