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斑马鱼胚胎/幼鱼对三(1,3-二氯-2-丙基)磷酸酯(TDCPP)的毒代基因组反应揭示了发育毒性的可能分子机制。

Toxicogenomic responses of zebrafish embryos/larvae to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) reveal possible molecular mechanisms of developmental toxicity.

机构信息

State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University , Nanjing, Jiangsu 210023, China.

出版信息

Environ Sci Technol. 2013 Sep 17;47(18):10574-82. doi: 10.1021/es401265q. Epub 2013 Aug 27.

Abstract

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is frequently present in indoor dust and can be detected in human milk. In order to evaluate the effects of TDCPP on vertebrate development, zebrafish embryos/larvae were used as an animal model to examine developmental phenotypes and explore possible mechanisms of toxicity by employing microarrays and iTRAQ labeling quantitative proteomics. The results demonstrated that treatment with TDCPP (3 μM) from 0.75 h postfertilization (hpf) inhibited cell rearrangement at 4 hpf, caused delay in epiboly at 5.7 and 8.5 hpf, and led to abnormal development (e.g., short tail, reduced body size) and lethality between 14 and 45 hpf, which might be related with altered expression of genes regulating embryogenesis. Furthermore, trunk curvature was observed as the main phenotype in 96 hpf zebrafish larvae exposed to 1 or 3 μM TDCPP, possibly by changing somite formation and expression of proteins related to fast muscle and cartilage development. Collectively, our results suggest that exposure to TDCPP causes developmental toxicity in vertebrates and warrant the need for studies to evaluate the potential health risks of TDCPP to developing human embryos/infants/children, due to its frequent presence in indoor dust and potential for human exposure.

摘要

磷酸三(1,3-二氯-2-丙基)酯(TDCPP)经常存在于室内灰尘中,并可在人乳中检测到。为了评估 TDCPP 对脊椎动物发育的影响,我们使用斑马鱼胚胎/幼鱼作为动物模型,通过微阵列和 iTRAQ 标记定量蛋白质组学来研究发育表型并探索其毒性的可能机制。结果表明,从受精后 0.75 小时(hpf)开始用 TDCPP(3 μM)处理,在 4 hpf 时抑制细胞重排,在 5.7 和 8.5 hpf 时导致胚外膜覆盖延迟,并导致 14 至 45 hpf 之间出现异常发育(例如短尾、体型减小)和致死性,这可能与调节胚胎发生的基因表达改变有关。此外,在暴露于 1 或 3 μM TDCPP 的 96 hpf 斑马鱼幼鱼中观察到躯干弯曲是主要表型,可能是通过改变体节形成和与快肌及软骨发育相关的蛋白质表达。总之,我们的研究结果表明,TDCPP 暴露会导致脊椎动物发育毒性,并且由于其在室内灰尘中的频繁存在和人类接触的可能性,需要研究来评估 TDCPP 对发育中人类胚胎/婴儿/儿童的潜在健康风险。

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