Li Vincent Wai Tsun, Tsui Mei Po Mirabelle, Chen Xueping, Hui Michelle Nga Yu, Jin Ling, Lam Raymond H W, Yu Richard Man Kit, Murphy Margaret B, Cheng Jinping, Lam Paul Kwan Sing, Cheng Shuk Han
State Key Laboratory in Marine Pollution, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, SAR, China.
Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, SAR, China.
Environ Sci Pollut Res Int. 2016 May;23(9):8275-85. doi: 10.1007/s11356-016-6180-9. Epub 2016 Feb 18.
The negative effects of overexposure to ultraviolet (UV) radiation in humans, including sunburn and light-induced cellular injury, are of increasing public concern. 4-Methylbenzylidene camphor (4-MBC), an organic chemical UV filter, is an active ingredient in sunscreen products. To date, little information is available about its neurotoxicity during early vertebrate development. Zebrafish embryos were exposed to various concentrations of 4-MBC in embryo medium for 3 days. In this study, a high concentration of 4-MBC, which is not being expected at the current environmental concentrations in the environment, was used for the purpose of phenotypic screening. Embryos exposed to 15 μM of 4-MBC displayed abnormal axial curvature and exhibited impaired motility. Exposure effects were found to be greatest during the segmentation period, when somite formation and innervation occur. Immunostaining of the muscle and axon markers F59, znp1, and zn5 revealed that 4-MBC exposure leads to a disorganized pattern of slow muscle fibers and axon pathfinding errors during the innervation of both primary and secondary motor neurons. Our results also showed reduction in AChE activity upon 4-MBC exposure both in vivo in the embryos (15 μM) and in vitro in mammalian Neuro-2A cells (0.1 μM), providing a possible mechanism for 4-MBC-induced muscular and neuronal defects. Taken together, our results have shown that 4-MBC is a teratogen and influences muscular and neuronal development, which may result in developmental defects.
过度暴露于紫外线(UV)对人体产生的负面影响,包括晒伤和光诱导的细胞损伤,日益引起公众关注。4-甲基亚苄基樟脑(4-MBC)是一种有机化学紫外线过滤剂,是防晒产品中的一种活性成分。迄今为止,关于其在脊椎动物早期发育过程中的神经毒性的信息很少。斑马鱼胚胎在胚胎培养基中暴露于不同浓度的4-MBC中3天。在本研究中,为了进行表型筛选,使用了高浓度的4-MBC,而目前环境中的环境浓度并未预期会出现这种情况。暴露于15μM 4-MBC的胚胎表现出异常的轴向弯曲,并表现出运动能力受损。发现暴露效应在体节形成和神经支配发生的分割期最为明显。对肌肉和轴突标记物F59、znp1和zn5进行免疫染色显示,4-MBC暴露会导致慢肌纤维的排列紊乱以及初级和次级运动神经元神经支配过程中的轴突寻路错误。我们的结果还表明,在胚胎体内(15μM)和体外哺乳动物Neuro-2A细胞(0.1μM)中,4-MBC暴露后乙酰胆碱酯酶(AChE)活性均降低,这为4-MBC诱导的肌肉和神经元缺陷提供了一种可能的机制。综上所述,我们的结果表明4-MBC是一种致畸剂,会影响肌肉和神经元发育,这可能导致发育缺陷。