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原油暴露激活核苷酸切除修复途径:从模式生物到河北溢油事件队列的转化研究。

Activation of the nucleotide excision repair pathway by crude oil exposure: A translational study from model organisms to the Hebei Spirit Oil Spill Cohort.

机构信息

School of Environmental Engineering, University of Seoul, 163 Siripdaero, Dongdaemun-gu, Seoul 02504, Republic of Korea.

Oil & POPs Research Group, Korea Institute of Ocean Science & Technology, Geoje, 53201, Republic of Korea; Ocean Science, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.

出版信息

Environ Pollut. 2019 Nov;254(Pt B):112997. doi: 10.1016/j.envpol.2019.112997. Epub 2019 Aug 6.

DOI:10.1016/j.envpol.2019.112997
PMID:31454576
Abstract

In order to gain insight into the human health implications of the Hebei Spirit Oil Spill (HSOS), the mechanism of toxicity of the Iranian heavy crude (IHC), the main oil component in the HSOS was investigated in Caenorhabditis elegans and zebrafish. The identified mechanism was translated to humans using blood samples from Taean residents, who experienced HSOS with different levels of exposure to the spill. C. elegans TF RNAi screening with IHC oil revealed the nucleotide excision repair (NER) pathway as being significantly involved by oil exposure. To identify the main toxicity contributors within the chemical mixture of the crude oil, further studies were conducted on C. elegans by exposure to C3-naphthalene, an alkylated polycyclic aromatic hydrocarbon (PAH), which constitutes one of the major components of IHC oil. Increased expression of NER pathway genes was observed following exposure to the IHC oil, C3-naphthalene enriched fraction and C3-naphthalene. As the NER pathway is conserved in fish and humans, the same experiment was conducted in zebrafish, and the data were similar to what was seen in C. elegans. Increased expression of NER pathway genes was observed in human samples from the high exposure group, which suggests the involvement of the NER pathway in IHC oil exposure. Overall, the study suggests that IHC oil may cause bulk damage to DNA and activation of the NER system and Alkylated PAHs are the major contributor to DNA damage. Our study provides an innovative approach for studying translational toxicity testing from model organisms to human health.

摘要

为了深入了解河北溢油事件(HSOS)对人类健康的影响,我们研究了伊朗重质原油(IHC)的毒性机制,这种原油是 HSOS 的主要成分之一,我们在秀丽隐杆线虫和斑马鱼中进行了研究。我们使用来自泰安市居民的血液样本,将鉴定出的机制转化为人类研究,这些居民经历了不同程度的溢油事件暴露。通过对 IHC 油进行秀丽隐杆线虫 TF RNAi 筛选,我们发现核苷酸切除修复(NER)途径在暴露于油中时会显著参与。为了确定原油化学混合物中的主要毒性贡献物,我们进一步在秀丽隐杆线虫中进行了研究,暴露于 C3-萘,一种烷基化多环芳烃(PAH),它是 IHC 油的主要成分之一。暴露于 IHC 油、C3-萘富分组分和 C3-萘后,观察到 NER 途径基因的表达增加。由于 NER 途径在鱼类和人类中是保守的,我们在斑马鱼中进行了相同的实验,数据与在秀丽隐杆线虫中观察到的相似。在高暴露组的人类样本中观察到 NER 途径基因的表达增加,这表明 NER 途径参与了 IHC 油的暴露。总的来说,该研究表明,IHC 油可能对 DNA 造成广泛损伤,并激活 NER 系统,而烷基化 PAHs 是 DNA 损伤的主要贡献者。我们的研究为从模式生物到人类健康的转化毒性测试提供了一种创新方法。

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