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Stage-dependent and regioselective toxicity of 2- and 6-hydroxychrysene during Japanese medaka embryogenesis
Aquatic Toxicology ( IF 4.1 ) Pub Date : 2021-03-02 , DOI: 10.1016/j.aquatox.2021.105791
Philip Tanabe , Constance A. Mitchell , Vanessa Cheng , Qiqing Chen , David C. Volz , Daniel Schlenk

Exposure to oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) at critical developmental time-points in fish models impairs red blood cell concentrations in a regioselective manner, with 2-hydroxychrysene being more potent than 6-hydroxychrysene. To better characterize this phenomenon, embryos of Japanese medaka (Oryzias latipes) were exposed to 2- or 6-hydroxychrysene (0.5, 2, or 5 μM) from 4 h-post-fertilization (hpf) to 7 d-post-fertilization. Following exposure, hemoglobin concentrations were quantified by staining fixed embryos with o-dianisidine (a hemoglobin-specific dye) and stained embryos were imaged using brightfield microscopy. Exposure to 2-hydroxychrysene resulted in a concentration-dependent decrease in hemoglobin relative to vehicle-exposed embryos, while only the highest concentration of 6-hydroxychrysene resulted in a significant decrease in hemoglobin. All tested concentrations of 2-hydroxychrysene also caused significant mortality (12.2 % ± 2.94, 38.9 % ± 14.4, 85.6 % ± 11.3), whereas mortality was not observed following exposure to 6-hydroxychrysene. Therefore, treatment of embryos with 2-hydroxychrysene at various developmental stages and durations was subsequently conducted to identify key developmental landmarks that may be targeted by 2-hydroxychrysene. A sensitive window of developmental toxicity to 2-hydroxychrysene was found between 52–100 hpf, with a 24 h exposure to 10 μM 2-hydroxychrysene resulting in significant anemia and mortality. Since exposure to 2-hydroxychrysene from 52 to 100 hpf, a window that includes liver morphogenesis in medaka, resulted in the highest magnitude of toxicity, liver development and function may have a role in 2-hydroxychrysene developmental toxicity.



中文翻译:

日本花aka胚胎发生过程中2-羟基和6-羟基丙烯的阶段依赖性和区域选择性毒性

在鱼类模型的关键发育时间点接触含氧多环芳烃(oxy-PAHs),会以区域选择性的方式损害红细胞的浓度,其中2-羟基ch比6-羟基ch更有效。为了更好地表征这种现象,从受精后4 h(hpf)到受精后7 d ,将日本(Oryzias latipes)的胚暴露于2-或6-羟基ch0.5、2或5μM)。暴露后,血红蛋白浓度通过用o染色固定的胚胎来定量-dianisidine(血红蛋白特异性染料)和染色的胚胎使用明场显微镜成像。相对于赋形剂暴露的胚胎,暴露于2-羟基hydroxy导致血红蛋白浓度依赖性降低,而只有最高浓度的6-羟基ch导致血红蛋白显着降低。所有测试浓度的2-羟基ch也引起显着的死亡率(12.2%±2.94,38.9%±14.4,85.6%±11.3),而暴露于6-羟基ch后未观察到死亡率。因此,随后在各个发育阶段和持续时间用2-羟基hydroxy处理胚胎,以鉴定可能被2-羟基ch靶向的关键发育标志。在52–100 hpf之间发现了对2-羟基hydroxy的发育毒性的敏感窗口,暴露于10μM2-羟基丙烯24小时会导致明显的贫血和死亡率。由于暴露于52至100 hpf的2-羟基ch(包括在medaka中的肝脏形态发生)的窗口会导致最高程度的毒性,因此肝脏的发育和功能可能在2-羟基ch的发育毒性中起作用。

更新日期:2021-03-12
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