中文摘要：

目的探讨叶酸缺乏与MTHFR C677T基因型多态性对乳腺癌患者淋巴细胞遗传损伤的影响及其与对照的差异。方法采用9天淋巴细胞长期培养辅以胞质阻断微核细胞组分析（CBMN cyt），分析不同浓度的叶酸对三种MTHFR C677T基因型乳腺癌人群和健康人群双核细胞微核率的影响与差异。结果MTHFR C677T三种基因型（CC，CT，TT）的乳腺癌个体与对照组淋巴细胞在叶酸浓度为30nmol／L时双核细胞微核率（MNBN）均显著高于60、120、240和2260nmol／L测试组（P〈0．001～0．05），60和120nmol／L两个测试组之间以及120、240和2260nmol／L三个测试组之间都未发现显著性差异。乳腺癌个体和对照组淋巴细胞中，MTHFR677TT在任何培养条件下，MNBN频率均显著高于相应样本组同类培养的野生纯合型（CC）（P〈0．01～0．05）；消减样本自身遗传损伤背景后，相同基因型的乳腺癌个体和正常个体淋巴细胞在MNBN频率上无显著性差异。结论在离体情况下，低于120nmol／L的叶酸浓度可增加人类淋巴细胞遗传损伤，无论是健康人群还是癌症患者，MTHFR6771TT型纯合个体，对叶酸缺乏都更加敏感。

英文摘要：

Objective To investigate the role of folate deficiency and MTHFR CA77T polymorphism on genetic damage in human lymphocytes from breast cancer cases and controls. Methods Lymphocytes with different MTHFR CA77T genotypes from the donors were cultured for 9 days in media with different concentrations of folic acid （FA） and the frequencies of micronucleated binucleated cell （MNBN） was evaluated by cytokinesis block micronucleus cytome assay （CBMN eyt）. Results The frequencies of micronucleated binueleated cell（MNBN） in 30 nmol/L FA were significantly higher than those in 60, 120, 240, 2 260 nmol/L FA （P〈0. 001-0. 05）, but no significant differences were observed either between those in 60 and 120 nmol/L FA, or between those in 120, 240 and 2 260 nmol/L FA within either groups when the genotype was the same. Within either of cancer case and control groups, the frequencies of MNBN of mutant homozygotes （TT） was significantly higher than that of wild isozygotes （CC） （P〈 0. 01-0. 05） in any FA concentration group. After the genetic damage background of sample was reduced, there was no significantly difference in MNBN frequency between lymphocytes with the same genotype from case and control at the same FA concentration. Conclusion FA concentration below 120 nmol/L increased genetic damage in human lymphocytes in vitro. Individuals with MTHFR 677TT genotype may be more sensitive to folic acid deficiency regardless the cancer statues than those with MTHFR 677CC and 677 CT genotypes.