环境中N-亚硝基化合物分子结构与致癌活性关系及其生物标志物研究

项目名称： 环境中N-亚硝基化合物分子结构与致癌活性关系及其生物标志物研究

项目编号： No.21277001

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 环境科学、安全科学

项目作者： 赵丽娇

作者单位： 北京工业大学

项目金额： 80万元

中文摘要： N-亚硝基化合物(NNCs)是环境中重要的致癌物质，其致癌风险评价和综合防治措施是环境化学和癌症防治研究领域中的关键问题。我们在前期工作中，对NNCs导致DNA损伤的作用机制及其分子结构与致癌活性关系进行了深入研究，已建立了NNCs构效关系和DNA损伤产物分析方法，阐明了NNCs致癌与抗癌机制的关键差异。在此基础上，本课题将采用理论化学方法研究NNCs的代谢活化和脱毒机制、不同代谢产物对DNA和蛋白的损伤机制、损伤的修复机制等，获取更广泛的结构参数；结合体外、细胞和动物实验水平上的NNCs代谢物及DNA和蛋白损伤产物的色谱-质谱定量分析，建立适用性更强、判对率更高的定量构效关系模型，并筛选出能够准确反应NNCs环境暴露水平的生物标志物。本课题将为深入揭示NNCs的环境危害水平、提出有效的NNCs致癌综合防治措施奠定基础；并将对环境污染标准和癌症高发区环境应对措施的制定具有重要意义。

中文关键词： N-亚硝基化合物；构效关系；致癌机理；DNA损伤及修复；生物标志物

英文摘要： N-nitroso compounds (NNCs) are important carcinogens existing in the environment. The risk assessment of the carcinogenesis of NNCs and their integrated control measures are key points in the fields of environmental chemistry and cancer prevention. In our previous works, we performed intensive investigations on the mechanism of DNA damages induced by NNCs, as well as the relationship between the molecular structure and carcinogenicity. The quantitative structural-activity relationship (QSAR) of NNCs and the analysis methodology for DNA damages were established. The critical distinction between the carcinogenic and anticancer mechanisms of NNCs was clarified. In this project, based on our previous achievements, we will explore the mechanisms for the activation and detoxification of NNCs, the mechanisms for DNA and protein damages induced by various NNCs metabolites, and the reparation of these DNA and protein damages, by using theoretical chemistry methods. The metabolites of NNCs and the damages of DNA and protein will be quantitatively analyzed in the samples from in vitro, cell lines and animal experiments by using chromatograph coupled with mass spectrometry. By combining the theoretical and experimental investigations, we expect to establish a QSAR model for NNCs with higher applicability and higher correct

英文关键词： N-nitroso comounds；Quantitative structure-activity relationship；Carcinogenic mechanism；DNA damage and repair；Biomarker