Men Shuhui, Xu Jiayun, Yang Zhanhong, Yan Zhenguang
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
Ningbo Clinical Pathology Diagnosis Center, Ningbo 315021, China.
Toxics. 2024 Nov 21;12(12):835. doi: 10.3390/toxics12120835.
DEHP is a plasticizer that is widely found in our water environment and poses a significant risk to the environment and human health. Long-term exposure to DEHP can cause endocrine disruption and interfere with the organism's normal functioning. In order to explore the potential effects of DEHP on the development of biological brain tissues, this study used bioinformatics analysis to confirm the diagnostic and prognostic value of PER3 in gliomas and further validated the neurotoxicity of DEHP using methods such as behavioral experiments and molecular biology in zebrafish. The experimental findings revealed that the expression level of PER3 in diseased tissues was significantly lower than that in the control group. In addition, the expression level of PER3 was significantly correlated with immune cell infiltration, immune checkpoint genes, and oncogenes. Moreover, the ROC curve analysis showed that PER3 could accurately differentiate between GBM tissues and adjacent normal tissues. To further validate the neurotoxicity of DEHP, we analyzed the effects of DEHP exposure on zebrafish development and PER3 expression by behavioral experiments and molecular biology. The results showed that exposure to DEHP substantially altered both the behavioral responses and the gene expression profiles within the brain tissues of zebrafish. PCR results indicate that the expression of circadian rhythm factor PER3 was significantly reduced in the brains of zebrafish in the exposed group, and circadian dysregulation had a certain promoting effect on the development of glioma. The aim of this work was to investigate the potential effects of DEHP contamination in a water environment on organism brain development. It was demonstrated that PER3 is an effective early diagnostic marker, which is of great significance in the diagnosis and clinical prognosis of glioma, and that DEHP exposure can lead to a significant reduction in PER3 expression in zebrafish brain tissue. This study further proved that DEHP has a potential carcinogenic effect, which adds scientific evidence to the carcinogenicity study of DEHP.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种增塑剂，在我们的水环境中广泛存在，对环境和人类健康构成重大风险。长期接触DEHP会导致内分泌紊乱，并干扰生物体的正常功能。为了探究DEHP对生物脑组织发育的潜在影响，本研究采用生物信息学分析来证实周期蛋白3（PER3）在胶质瘤中的诊断和预后价值，并利用行为实验和分子生物学等方法在斑马鱼中进一步验证DEHP的神经毒性。实验结果显示，患病组织中PER3的表达水平显著低于对照组。此外，PER3的表达水平与免疫细胞浸润、免疫检查点基因和癌基因显著相关。而且，ROC曲线分析表明，PER3能够准确区分胶质母细胞瘤（GBM）组织和相邻正常组织。为了进一步验证DEHP的神经毒性，我们通过行为实验和分子生物学分析了DEHP暴露对斑马鱼发育和PER3表达的影响。结果表明，暴露于DEHP会显著改变斑马鱼脑组织内的行为反应和基因表达谱。PCR结果表明，暴露组斑马鱼大脑中昼夜节律因子PER3的表达显著降低，昼夜节律失调对胶质瘤的发展有一定的促进作用。这项工作的目的是研究水环境中DEHP污染对生物体脑发育的潜在影响。结果表明，PER3是一种有效的早期诊断标志物，在胶质瘤的诊断和临床预后中具有重要意义，并且DEHP暴露可导致斑马鱼脑组织中PER3表达显著降低。本研究进一步证明DEHP具有潜在致癌作用，为DEHP的致癌性研究增添了科学依据。
