基于体外仿生模型探究卤代苯系液晶单体在代谢过程中的毒性转变规律

我国是LCMs的生产和消费大国，同时，我国还是世界废弃电子产品主要拆解地之一。废弃显示屏经机械破碎后，利用热分解或化学清洗等方法提取贵金属，往往没有针对LCMs的后续处理处置措施，这极大的增加了液晶材料等有毒有害物质进入环境的可能性。因此，在我国针对LCMs开展研究具有重要的社会意义。基于此，我们团队于2018年(ES&T，2018)，通过对10余家LCMs生产厂家实地调研，获取了一份包含331种市售LCMs清单，采用美国环境保护署（USEPA）开发的EPI软件，对其环境持久性、生物蓄集性和生物毒性（PBT）进行了预测，结果显示，80种HB-LCMs进入环境后表现出PBT特性，这一结果发表在环境领域顶级期刊ES&T上。尽管形势严峻，但除此之外，还未见任何关于HB-LCMs环境毒理化学方面的研究，科学数据严重匮乏。本课题拟以HB-LCMs为目标物质，其核心思想是基于野外环境生物，利用精密肝切片技术可完整保存肝组织结构和生物酶系的特点，从而在保持细胞间联系和两相酶系(I和II)完整的前提下，揭示HB-LCMs的生物转化规律，以及由代谢所引起的毒性转变规律。具体研究内容分解如下：识别长江下游及太湖生物HB-LCMs污染特征、建立基于精密肝组织切片的体外仿生模型、解析HB-LCMs的两相代谢规律、揭示其在生物代谢过程中致肝毒性增强/消减的转变规律。本项目可为污染物代谢研究提供一种更接近体内环境的研究方法，亦对HB-LCMs生态风险评估具有重要的实际意义。

Halogenated benzene-liquid crystal monomers (HB-LCMs) have been largely produced and widely used in China. Our recent study demonstrated that HB-LCMs would exhibit properties of persistence, bioaccumulation and toxicity after entering into the natural environments. However, there is dearth of studies on the environmental occurrences and hazards of HB-LCMs. By use of precision-cut liver slice technique, our present study will develop an in vitro metabolism model which can preserve complete structure of liver tissue and phase I and II biological enzymes as possible. The developed model will be finally used for investigation of mechanism of metabolism and hepatoxicity of environmental contaminants. In this study, detailed tasks are described following as: 1) characterization the profiles of contamination of HB-LCMs in aquatic organisms from Tai Lake; 2) establishment of a biomimetic model based on precision-cut liver slice technique; 3) investigation of mechanism of metabolism of HB-LCMs; and 4) evaluation of hepatotoxicity of HB-LCMs and their metabolites. Collectively, our present study has two outcomes: 1) a novel biomimetic in vitro model, which will be a great addition for examining the mechanism of metabolism of environmental contaminants, and 2) understanding the metabolic pathways and toxicity shifting of HB-LCMs, which is critical for ecological risk assessment of these novel environmental contaminants.