Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan 430056, China; School of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology, Wuhan 430025, China.
Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan 430056, China.
Aquat Toxicol. 2020 Aug;225:105525. doi: 10.1016/j.aquatox.2020.105525. Epub 2020 Jun 23.
Halogenated dipeptides, 3, 5-di-I-tyrosylalanine (DIYA), have been identified as novel disinfection byproducts (DBPs), following chloramination of authentic water. However, little is known about their toxicity. Zebrafish embryos were used to assess the toxicity of novel iodinated DBPs (I-DBPs). Although DIYA did not exhibit high acute toxicity to embryonic zebrafish (LC > 2 mM), it significantly inhibited pigmentation of melanophores and xanthophores on head, trunk and tail at 500 μM as determined by photographic analysis. Whereas N-phenylthiourea (PTU) as a pigment inhibitor did not inhibit development of yellow pigments. Colorimetric detection of melanin further confirmed these results. Quantitative real time polymerase chain reaction (qRT-PCR) measurements indicated that genes (dct, slc24a5, tyr, tyrp1a, tyrp1b, silva) associated with the melanogenesis pathway were dramatically down-regulated following exposure to 500 μM DIYA. In addition, enzymatic activity of tyrosinase (TYR) decreased, also demonstrating that the underlying mechanism of hypopigmentation was attributed to the disruption of melanogenesis pathway. Transcription levels of xanthophore genes (gch2, bnc2, csf1a, csf1b, pax7a and pax7b) were also monitored by qRT-PCR assay. DIYA exposure up-regulated expression of gch2 and bnc2, but not csf1 and pax7. Tested DIYA analogues, brominated tyrosine was unlikely to inhibit pigmentation, indicating that the iodine substitution and dipeptides structure are of important structural feature for the inhibition of pigmentation. In this study, we observed that DIYA inhibited melanogenesis related genes, which might contribute to pigmentation defects. Moreover, as an emerging I-DBPs, the developmental toxicity of aromatic dipeptides should be further studied.
卤代二肽，3,5-二碘酪氨酸（DIYA），在对真实水样进行氯胺化后被鉴定为新型消毒副产物（DBPs）。然而，人们对其毒性知之甚少。本研究采用斑马鱼胚胎模型来评估新型碘代 DBPs（I-DBPs）的毒性。虽然 DIYA 对斑马鱼胚胎的急性毒性较低（LC > 2 mM），但在 500 μM 浓度下，通过照相分析发现，其显著抑制了头部、躯干和尾部黑素细胞和黄色素细胞的色素沉着。而作为一种色素抑制剂的 N-苯硫脲（PTU）并不抑制黄色素的发育。黑色素的比色检测进一步证实了这些结果。实时定量聚合酶链反应（qRT-PCR）测量表明，暴露于 500 μM DIYA 后，与黑色素生成途径相关的基因（dct、slc24a5、tyr、tyrp1a、tyrp1b、silva）显著下调。此外，酪氨酸酶（TYR）的酶活性也降低，这也表明色素减退的潜在机制归因于黑色素生成途径的破坏。通过 qRT-PCR 分析还监测了黄色素细胞基因（gch2、bnc2、csf1a、csf1b、pax7a 和 pax7b）的转录水平。DIYA 暴露上调了 gch2 和 bnc2 的表达，但不影响 csf1 和 pax7。此外，对测试的 DIYA 类似物进行研究，发现溴代酪氨酸不太可能抑制色素沉着，表明碘取代和二肽结构是抑制色素沉着的重要结构特征。在这项研究中，我们观察到 DIYA 抑制了与黑色素生成相关的基因，这可能导致色素沉着缺陷。此外，作为一种新兴的 I-DBPs，芳香二肽的发育毒性应进一步研究。
