Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example.
Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example.
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DOI：
10.3390/toxics10070351
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发表时间：
2022-06-27
期刊：
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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城市环境受到人为挥发性有机化合物（VOC）的复杂混合物的困扰，例如苯、甲苯、乙烯和二甲苯（BTEX）的混合物。导致人类接触苯系物的来源包括汽车尾气、工业排放、建筑材料的废气以及石油溢出和泄漏。在苯系物混合物中，苯是挥发性最强的化合物，与许多不良健康后果有关。然而，很少有研究关注低水平苯对早期发育过程中暴露的影响，这是血液学，免疫，代谢和解毒系统不成熟时的易感窗口。在这项研究中，我们使用斑马鱼进行VOC暴露模型和评估表型和转录组反应0.1和1 ppm苯暴露在胚胎发育的前五天（n = 740每治疗）。暴露浓度为1 ppm的斑马鱼幼鱼池中的苯体负荷为2 mg/kg，暴露浓度为0.1 ppm的鱼体内的苯体负荷低于检测限。没有观察到的表型变化，发现在这两个幼虫，除了显着的骨骼畸形0.1 ppm暴露的鱼（p = 0.01）相比，未暴露的鱼。基于转录组学反应，1 ppm苯涉及血液系统发育、氧化应激反应、脂肪酸代谢、免疫系统和炎症反应的调节的失调基因，包括来自细胞色素P450基因家族的apob、nfkbiaa、serpinf 1、foxa 1、cyp 2k 6和cyp 2n 13。关键基因包括pik 3c 2b，pltp和chia.2在1 ppm和0.1 ppm暴露中差异表达。然而，与1 ppm相比，0.1 ppm诱导的转录组学变化较少。未来的研究需要确定胚胎发生过程中的这些转录组反应在等于或低于1 ppm的水平下是否具有长期后果。
Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil spillage and leakage. Among the BTEX mixture, benzene is the most volatile compound and has been linked to numerous adverse health outcomes. However, few studies have focused on the effects of low-level benzene on exposure during early development, which is a susceptible window when hematological, immune, metabolic, and detoxification systems are immature. In this study, we used zebrafish to conduct a VOC exposure model and evaluated phenotypic and transcriptomic responses following 0.1 and 1 ppm benzene exposure during the first five days of embryogenesis (n = 740 per treatment). The benzene body burden was 2 mg/kg in 1 ppm-exposed larval zebrafish pools and under the detection limit in 0.1 ppm-exposed fish. No observable phenotypic changes were found in both larvae except for significant skeletal deformities in 0.1 ppm-exposed fish (p = 0.01) compared with unexposed fish. Based on transcriptomic responses, 1 ppm benzene dysregulated genes that were implicated with the development of hematological system, and the regulation of oxidative stress response, fatty acid metabolism, immune system, and inflammatory response, including apob, nfkbiaa, serpinf1, foxa1, cyp2k6, and cyp2n13 from the cytochrome P450 gene family. Key genes including pik3c2b, pltp, and chia.2 were differentially expressed in both 1 and 0.1 ppm exposures. However, fewer transcriptomic changes were induced by 0.1 ppm compared with 1 ppm. Future studies are needed to determine if these transcriptomic responses during embryogenesis have long-term consequences at levels equal to or lower than 1 ppm.
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DOI：
10.1038/nrm3772
发表时间：
2014-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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IκBα的后期合成可隔离巨噬细胞中的非规范NF-κB信号传导TLR4激活的规范NF-κB途径。
影响因子：
7.3
作者：
Chatterjee B;Banoth B;Mukherjee T;Taye N;Vijayaragavan B;Chattopadhyay S;Gomes J;Basak S
通讯作者：
Basak S
影响因子：
10.4
作者：
Gut, I;Nedelcheva, V;Tichavska, B
通讯作者：
Tichavska, B
影响因子：
29.4
作者：
Goessling W;Sadler KC
通讯作者：
Sadler KC
影响因子：
2.6
作者：
Cho, Woo Sung;Kim, Tae Hoon;Lee, Sang Hag
通讯作者：
Lee, Sang Hag