叶酸和核黄素对乳腺癌患者淋巴细胞8和17号染色体非整倍体的影响

目的： 探讨叶酸和核黄素对乳腺癌患者外周血淋巴细胞8和17号染色体非整倍体的影响。方法：采用多色荧光原位杂交 (FISH)比较乳腺癌患者与对照组淋巴细胞在叶酸高 (200 nmol/L，HF)、低 (20 nmol/L，LF)浓度和核黄素高 (500 nmol/L，HR)、低 (1 nmol/L，LR)浓度不同组合 (LFLR，LFHR，HFLR，HFHR)下，8和17号染色体在单核细胞及胞质阻断双核细胞中非整倍体的发生频率及其差异。结果：乳腺癌及对照组在高叶酸组合 (HFLR+HFHR)培养条件下8和17号染色体单、双核细胞异常信号数总和均显著低于低叶酸组合 (LFLR+LFLR) (P<0.01)。在各组合浓度下，两条染色体的异常信号频率总和在单核和双核细胞中，乳腺癌患者均较对照组显著增高 (P<0.01)。叶酸和乳腺癌因素对两条染色体的异常分离均有显著影响 (P<0.01)，但叶酸缺乏的影响强于乳腺癌因素；核黄素缺乏与乳腺癌因素对两条染色体分离的变异贡献率差异无统计学意义 (P>0.05)。结论：叶酸缺乏可能导致8和17号染色体形成非整倍体，在本研究体系中叶酸缺乏是影响染色体正常分离的主导因素。

The effect of folate and riboflavin on chromosomes 8 and 17 aneuploidy in lymphocytes of breast cancer patients and normal controls

OBJECTIVE:The research was to test the effect of folate (FA) and riboflavin (RF) on chromosome 8 and 17 aneuploidy in lymphocytes of breast cancer patients and normal controls. METHODS：Lymphocytes were cultured in each of the four media：high (200 nmol/L，HF) and low (20 nmol/L，LF) FA，high (500 nmol/L，HR) and low (1 nmol/L，LR) RF media (LFLR，LFHR，HFLR，HFHR). Chromosomes 8 and 17 aneuploidy was measured in mononucleated (MONO) and cytokinesis-blocked binucleated (BN) cells using dual-color ?uorescence in situ hybridization (FISH). RESULTS：In lymphocytes of breast cancer subjects and controls，LF media (LFLR or LFHR) induced significant and similar increases in frequencies of aneuploidy of chromosomes 8 and 17 relative to culture in HF media (HFLR or HFHR) (P<0.01). The frequency of 8 and 17 aneuploidy in breast cancer subjects was significantly higher than those of normal controls (P<0.01). FA and breast cancer status had significant impact on the frequency of aneuploidy (P<0.01)，while effect of FA was stronger deficiency. RF deficiency partially affected chromosome segregation，but not significantly (P>0.05).CONCLUSION：FA deficiency is a possible cause of chromosome 8 and 17 aneuploidy. FA is the dominant factor that affects chromosome segregation in our experimental system.