项目名称： 基于质谱技术的双酚A与DNA加合物检测方法的研究及其应用

项目编号： No.21505111

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 赵洪芝

作者单位： 香港浸会大学深圳研究院

项目金额： 21万元

中文摘要： 双酚A（BPA）是一种广泛应用于塑料制造的化工原料，报道表明BPA可能增加癌症风险，但其机理尚不明确。DNA加合物是DNA化学损伤中最重要与最普遍的形式，可反映毒物到达靶位的实际接触剂量及DNA的损伤程度，对其分析有助于毒性机理的阐明。本项目拟建立基于质谱技术的快速、便捷、高通量、高灵敏度的BPA-DNA加合物的测定方法，并运用此方法分别分析4种不同细胞系及成年SD大鼠经不同剂量、不同时间的BPA暴露后所形成的BPA-DNA加合物。通过比较肿瘤细胞与正常细胞产生的BPA-DNA加合物的差异，探寻BPA可能的潜在致癌机理。通过BPA-DNA加合物在大鼠尿液、血液及不同组织中的形成情况，明确其在大鼠体内的组织分布和代谢情况。通过研究BPA-DNA加合物随BPA暴露时间、剂量的变化情况，筛选和确认可靠的肿瘤效应标志物，为BPA的毒性机理研究提供基础依据，为BPA与癌症风险相关性研究提供信息。

中文关键词： 双酚A；DNA加合物；液相色谱-质谱联用；定性定量分析

英文摘要： Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastics and other products. It has been reported that the BPA exposure may be associated with an increased risk cancer. However, the mechanism of increasing risk of cancer induced by the BPA exposure has not been reported clearly. DNA adducts is the most important chemical and the most important and commonly mode of DNA damage. Detection of DNA adduct can provide the exact interior dosage and help to illuminate the toxicology mechanism. This proposal aims to establish a rapid, high-throughput, and sensitive method base on mass spectrometry (MS) for characterization and determination of BPA-DNA adducts. High resolution and sensitivity MS will be applied for the characterization and quantitative determination of DNA adducts. The BPA-DNA adducts in four type cell lines and adult SD rats will be analyzed after BPA explore in different explore dose and time of BPA. The BPA-DNA adducts in cancer cell and normal cell will be compared. BPA-DNA adducts in urine, plasma, and tissues (eg. liver, kidney, and spleen) of SD rat will be detected by using this method to discover their metabolism and distribution in rat tissue. The relationship between DNA adducts content and exposed dose will also be investigated which is for screening and confirmation reliable marker of cancer. The obtained results will provide useful information for future investigation on BPA toxicities and the mechanism of toxicity of BPA. The content of BPA-DNA adducts in rat urine, plasma, and different tissues will be compared to know the metabolism and tissue distribution. Furthermore, the relationship between DNA adducts content and exposed dose will be investigated to screening and confirmation reliable marker of cancer. The obtained results will provide useful information the mechanism of toxicity of BPA and the relation between BPA and cancer risk.

英文关键词： Bisphenol A (BPA);DNA adducts;Liquid chromatograph-Mass spectrometry (LC-MS);Qualitative and quantitative analysis