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核糖体生物合成途径作为邻苯二甲酸苄基丁酯(BBP)对摇蚊幼虫毒性作用的早期靶点。

The ribosome biogenesis pathway as an early target of benzyl butyl phthalate (BBP) toxicity in Chironomus riparius larvae.

作者信息

Herrero Óscar, Planelló Rosario, Morcillo Gloria

机构信息

Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a Distancia, UNED, Paseo de la Senda del Rey 9, 28040 Madrid, Spain.

出版信息

Chemosphere. 2016 Feb;144:1874-84. doi: 10.1016/j.chemosphere.2015.10.051. Epub 2015 Nov 11.

DOI:10.1016/j.chemosphere.2015.10.051
PMID:26539713
Abstract

Butyl benzyl phthalate (BBP) is a ubiquitous contaminant whose presence in the environment is expected for decades, since it has been extensively used worldwide as a plasticizer in the polyvinyl chloride (PVC) industry and the manufacturing of many other products. In the present study, the interaction of BBP with the ribosome biogenesis pathway and the general transcriptional profile of Chironomus riparius aquatic larvae were investigated by means of changes in the rDNA activity (through the study of the internal transcribed spacer 2, ITS2) and variations in the expression profile of ribosomal protein genes (rpL4, rpL11, and rpL13) after acute 24-h and 48-h exposures to a wide range of BBP doses. Furthermore, cytogenetic assays were conducted to evaluate the transcriptional activity of polytene chromosomes from salivary gland cells, with special attention to the nucleolus and the Balbiani rings (BRs) of chromosome IV. BBP caused a dose and time-dependent toxicity in most of the selected biomarkers, with a general depletion in the gene expression levels and the activity of BR2 after 48-h treatments. At the same time, decondensation and activation of some centromeres took place, while the activity of nucleolus remained unaltered. Withdrawal of the xenobiotic allowed the larvae to reach control levels in the case of rpL4 and rpL13 genes, which were previously slightly downregulated in 24-h tests. These data provide the first evidence on the interaction of BBP with the ribosome synthesis pathways, which results in a significant impairment of the functional activity of ribosomal protein genes. Thus, the depletion of ribosomes would be a long-term effect of BBP-induced cellular damage. These findings may have important implications for understanding the adverse biological effects of BBP in C. riparius, since they provide new sensitive biomarkers of BBP exposure and highlight the suitability of this organism for ecotoxicological risk assessment, especially in aquatic ecosystems.

摘要

邻苯二甲酸丁苄酯(BBP)是一种普遍存在的污染物,鉴于其在全球范围内被广泛用作聚氯乙烯(PVC)行业及许多其他产品制造中的增塑剂,预计它会在环境中存在数十年。在本研究中,通过急性暴露24小时和48小时后,研究rDNA活性的变化(通过对内部转录间隔区2,即ITS2的研究)以及核糖体蛋白基因(rpL4、rpL11和rpL13)表达谱的变化,来探究BBP与摇蚊水生幼虫核糖体生物合成途径及总体转录谱的相互作用。此外,进行了细胞遗传学分析以评估唾液腺细胞多线染色体的转录活性,特别关注核仁及四号染色体的巴尔比亚尼环(BRs)。BBP在大多数选定的生物标志物中引起了剂量和时间依赖性毒性,48小时处理后基因表达水平普遍下降,BR2活性降低。与此同时,一些着丝粒发生解聚和激活,而核仁活性保持不变。去除外源化合物后,rpL4和rpL13基因在幼虫中恢复到对照水平,这两个基因在24小时试验中先前略有下调。这些数据首次证明了BBP与核糖体合成途径的相互作用,这导致核糖体蛋白基因的功能活性受到显著损害。因此,核糖体的减少将是BBP诱导细胞损伤的长期效应。这些发现对于理解BBP对摇蚊的不利生物学影响可能具有重要意义,因为它们提供了新的BBP暴露敏感生物标志物,并突出了这种生物在生态毒理学风险评估中的适用性,特别是在水生生态系统中。

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