Integrated biological responses and tissue-specific expression of p53 and ras genes in marine mussels following exposure to benzo(a) pyrene and C60 fullerenes, either alone or in combination
Integrated biological responses and tissue-specific expression of p53 and ras genes in marine mussels following exposure to benzo(a) pyrene and C60 fullerenes, either alone or in combination
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DOI：
10.1093/mutage/gew049
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发表时间：
2017-01-01
期刊：
影响因子：
2.7
通讯作者：
Jha, Awadhesh N.
中科院分区：
文献类型：
--
作者：
Di, Yanan;Aminot, Yann;Jha, Awadhesh N.
我们使用海洋双壳贝类(Mytilus Gallopecialis)来评估暴露于模型工程纳米颗粒C-60富勒烯后的一系列生物或生物标记物反应，无论是单独接触还是与模型多环芳烃苯并(α)芘[B(α)P]结合使用。使用的综合生物标志物方法包括：(I)测定‘清除率’(个体水平的生理指标)，(Ii)组织病理学改变(在组织水平)，(Iii)使用彗星分析(在细胞水平)DNA链断裂，以及(Iv)通过实时定量聚合酶链式反应(在分子/遗传水平)测定p53(抑癌基因)和ras(癌基因)的转录改变。此外，还测量了消化腺中的总谷胱甘肽作为氧化应激的替代指标。在这里，我们报告了贻贝在暴露1天后没有表现出显著的‘清除率’变化，但是在暴露3天后发现‘清除率’显著增加。所选器官(即鳃、消化腺、内收肌和外套膜)的组织病理学显示，所有组织类型的异常发生率都有所增加，尽管并不是所有暴露的生物体都表现出这些异常。值得注意的是，大多数受试者在暴露3天后发现DNA链断裂水平增加。此外，尽管与其他生物标记物相比，个体间的大量差异明显，但在组织和化学特异性模式中观察到了对p53和ras表达的显著诱导。总体而言，不同水平的生物反应表现出不同的敏感性，其中DNA链断裂和基因表达变化表现出更高的敏感性。此外，观察到的遗传毒性反应在恢复期后是可逆的，这表明在我们的实验条件下，贻贝能够应对毒物C-60和/或B(α)P。总体而言，在这项全面的研究中，我们证明贻贝是一个合适的海洋无脊椎动物模式物种，以研究可能的遗传毒物和毒物单独或组合在不同生物组织水平(即从分子到个体水平)所引起的潜在有害影响。
We used the marine bivalve (Mytilus galloprovincialis) to assess a range of biological or biomarker responses following exposure to a model-engineered nanoparticle, C-60 fullerene, either alone or in combination with a model polycyclic aromatic hydrocarbon, benzo(alpha) pyrene [B(alpha) P]. An integrated biomarker approach was used that included: (i) determination of 'clearance rates' (a physiological indicator at individual level), (ii) histopathological alterations (at tissue level), (iii) DNA strand breaks using the comet assay (at cellular level) and (iv) transcriptional alterations of p53 (anti-oncogene) and ras (oncogene) determined by real-time quantitative polymerase chain reaction (at the molecular/genetic level). In addition, total glutathione in the digestive gland was measured as a proxy for oxidative stress. Here, we report that mussels showed no significant changes in 'clearance rates' after 1 day exposure, however significant increases in 'clearance rates' were found following exposure for 3 days. Histopathology on selected organs (i. e. gills, digestive glands, adductor muscles and mantles) showed increased occurrence of abnormalities in all tissues types, although not all the exposed organisms showed these abnormalities. Significantly, increased levels of DNA strand breaks were found after exposure for 3-days in most individuals tested. In addition, a significant induction for p53 and ras expression was observed in a tissue and chemical-specific pattern, although large amounts of inter-individual variability, compared with other biomarkers, were clearly apparent. Overall, biological responses at different levels showed variable sensitivity, with DNA strand breaks and gene expression alterations exhibiting higher sensitivities. Furthermore, the observed genotoxic responses were reversible after a recovery period, suggesting the ability of mussels to cope with the toxicants C-60 and/or B(alpha) P under our experimental conditions. Overall, in this comprehensive study, we have demonstrated mussels as a suitable model marine invertebrate species to study the potential detrimental effects induced by possible genotoxicants and toxicants, either alone or in combinations at different levels of biological organisation (i. e. molecular to individual levels).