【作者】 胡洁；

【导师】 陈灵；

【作者基本信息】 上海交通大学 ， 生物化工， 2007， 硕士

【摘要】 马兜铃酸存在于65种以上的马兜铃科植物中,其中有许多曾用于传统中药、食品补充剂或草药疗法减肥。近年来,人们发现马兜铃酸是一种对人和动物都有致突变性的强致癌剂。在之前的研究中,我们发现马兜铃酸是一种强致突变剂,对小鼠淋巴瘤细胞有显著的细胞毒性和致突变作用。本研究中我们进一步阐明马兜铃酸(Aristolochic Acid, AA)的致突变分子机制,本试验采用“小鼠淋巴瘤细胞L5178Y/TK+/-致突变检测方法”(L5178Y/TK+/- Mouse Lymphoma Mutation Assay,MLA)来获得胸苷激酶基因(tk)突变克隆。为了检测含功能性tk基因的11号染色体(11b)上DNA断裂情况,我们挑取对照组和100μg/ml AA处理小鼠淋巴瘤L5178Y tk+/--3.7.2-细胞得到的tk基因突变克隆,提取DNA,用基于PCR的杂合性缺失(Loss of heterozygosity,LOH)的分析方法考察11号染色体上分布的tk位点和其他三个微卫星位点(D11Mit42, D11Mit29, D11Mit74)的杂合性缺失情况。从检测结果来看100μg/ml AA诱导的突变体中功能性tk基因缺失率为更多还原

【Abstract】 Aristolochic acid (AA) is contained in at least 65 different kind of Aristolochiaceae plants, many of which were used as traditional Chinese medicines or as dietary complementary or herbal remedies for weight-loss. It is a potent carcinogens that has been found to be mutagenic in humans and animals for several years. In the previous study, we have found that AA is a potent mutagen which can induce significant cytotoxic and mutagenic effects on mouse lymphoma cells. In this study, we elucidate molecular mechanism of mutagenic effects which are induced by Aristolochic Acid in L5178Y tk+/--3.7.2- mouse lymphoma cells. We used L5178Y/TK+/- Mouse Lymphoma Assay (MLA) to gain tk mutants. To indentify the clastogenic events on the tk+ bearing chromosome 11b, we analyzed DNA isolated from tk mutants from control and 100μg/ml treatment group by a PCR-based method to detect loss of heterozygosity (LOH) on Tk1 locus and the更多还原