中文摘要：

目的为研究马兜铃酸（Aristolochic Acid，AA）的致突变机制提供实验依据。方法挑取对照组和100μg/ml从处理小鼠淋巴瘤LS178Y tk^＋/--3．7．2-细胞得到的胸苷激酶（Thymidine kinase，tk）基因突变克隆，提取DNA，用基于PCR的杂合性缺失（Loss of heterozygosity，LOH）的分析方法检测含功能性tk基因（tk^＋）的11号染色体（11b）上的断裂情况。结果100μg／ml从诱导的突变体中tk^＋基因缺失率为99．01％，其中所有的小克隆（Small Clone，SC）都失去了tk^＋基因，而大克隆（Large Clone，Lc）的LOH发生率为96．6％。进一步分析11号染色体上的分布的3个微卫星位点（D11 Mit42，D11Mit29，D11Mit74）的LOH状况如下：6cm长度的DNA断裂频率为76％，38cm长度DNA即超过染色体一半长度的DNA断裂频率为34％，整条染色体的缺失率为16％。另外LC在3个微卫星位点（D11Mit42，D11Mit29，D11Mit74）上的LOH发生率分别是：88％，60％和24％；SC的分别为：64％，8％和8％。结论从是一个强染色体断裂剂。在11b染色体上LC的染色体断裂情况比LC严重。

英文摘要：

Objective To elucidate the mutngenic effects of aristolochic acid（AA） on the tk ^＋/- locus of 1-5178Y tk ^＋/- -3.7.2- mouse lymphoma cells. Methods DNA isolated from tit mutants in the control group and 100 μg/ml AA treatment group were analyzed by a PCR-based method to detect loss of beterozygosity （LOH） and identify the clastogenic events on the tk^＋ -bearing chromosome 11 b. Results The total percentage of LOH in mutants induced by 100 μg/ml AA was 99.01% ; All the small colony mutants had lost the tklb allele, while the frequency of LOH in large colony mutants was 96.6% . The percentage of LOH on the other three microsatellite loci （D11Mit42, D11Mit29, D11Mit74） distributed along chromosome lib was further analyzed. 76% of mutants showed damage that reach to 6 centimorgan（cm） in the chromosome length; 34% of mutants had a damage of DNA reached 38 cm which was larger than half of chromosome 11; 16% of mutants had lost the entire chromosome. The percentage of LOH at the three loci in large colony mutants were 88%, 60%, 24% respectively, while in small colony mutants those were 64%, 8%, 8%. Conclusion AA is a strong clastogen. The damage of DNA on chromosome llb induced by AA in large colonies seemed more extensive than that in small colonies.