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组织特异性表达的 p53 和 ras 基因对环境遗传毒物苯并(α)芘在海洋贻贝类。

Tissue-specific expression of p53 and ras genes in response to the environmental genotoxicant benzo(α)pyrene in marine mussels.

机构信息

School of Biomedical and Biological Sciences, University of Plymouth, Drake Circus, Plymouth, Devon PL4 8AA, UK.

出版信息

Environ Sci Technol. 2011 Oct 15;45(20):8974-81. doi: 10.1021/es201547x. Epub 2011 Sep 27.

DOI:10.1021/es201547x
PMID:21899289
Abstract

Marine mussels can develop hemeic and gonadal neoplasia in the natural environment. Associated with these diseases are the tumor suppressor (TS) p53 and the proto-oncogene ras coded proteins, both of which are highly conserved among molluscs and vertebrates. We report, for the first time, tissue-specific expression analysis of p53 and ras genes in Mytilus edulis by means of quantitative RT-PCR. A tissue-specific response was observed after 6 and 12 days exposure to a sublethal concentration of a model Polycyclic Aromatic Hydrocarbon (PAH), benzo(α)pyrene (B(α)P). This sublethal concentration (56 μg/L) was selected based on an integrated biomarker analysis carried out prior to gene expression analysis, which included a 'clearance rate' assay, histopathological analysis, and DNA strand break measurements. The results indicated that the selected concentration of B(α)P can lead to the induction of DNA strand breaks, tissue damage, and expression of tumor-regulating genes. Both p53 and ras are expressed in a tissue-specific manner, which collaborate with tissue-specific function in response to genotoxic stress. The integrated biological responses in Mytilus edulis strengthen the use of this organism to investigate the fundamental mechanism of development of malignancy in invertebrate which could be translated to other organisms including humans.

摘要

海洋贻贝在自然环境中可能会患上血红素和性腺肿瘤。与这些疾病相关的是肿瘤抑制基因 (TS) p53 和原癌基因 ras 编码蛋白,这两种蛋白在软体动物和脊椎动物中高度保守。我们首次通过定量 RT-PCR 报告了贻贝组织中 p53 和 ras 基因的组织特异性表达分析。在亚致死浓度的多环芳烃(PAH)苯并(α)芘(B(α)P)暴露 6 天和 12 天后,观察到组织特异性反应。该亚致死浓度(56 μg/L)是基于基因表达分析之前进行的综合生物标志物分析选择的,其中包括“清除率”测定、组织病理学分析和 DNA 链断裂测量。结果表明,所选浓度的 B(α)P 可导致 DNA 链断裂、组织损伤和肿瘤调节基因的表达。p53 和 ras 都以组织特异性方式表达,它们与组织特异性功能协同作用,以应对遗传毒性应激。贻贝的综合生物学反应增强了利用该生物体来研究无脊椎动物恶性肿瘤发生的基本机制的能力,这些机制可能会转化为包括人类在内的其他生物体。

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