摘要
目的:探讨不同还原态叶酸和胆碱对人结肠腺癌细胞DNA错配修复基因h MLH1和h MSH2转录水平的影响。方法:根据受试物在生理和离体情形下维持人基因组结构稳定的最适浓度,以含15、30、120 nmol/L的氧化型叶酸(FA)或还原型叶酸(5-Me THF)与12μmol/L氯化胆碱(CC)组合,以及不同浓度CC(1.5、3μmol/L)与120 nmol/L FA组合的修饰RPMI-1640培养基,对人结肠腺癌细胞株COLO205进行20 d干预培养。以实时荧光定量PCR检测h MLH1和h MSH2 m RNA水平。结果:受试细胞株h MLH1和h MSH2 m RNA水平与FA、5-Me THF和CC浓度呈显著负相关(P<0.01或P<0.05)。30和120 nmol/L浓度下,5-Me THF对上述细胞h MLH1和h MSH2转录水平的影响显著强于同等浓度的FA(P<0.01或P<0.05)。结论:FA、5-Me THF和CC缺乏可上调结肠腺癌细胞h MLH1和h MSH2转录水平,这可能是细胞对叶酸和胆碱缺乏导致的DNA损伤和异常甲基化的应答反应。
OBJECTIVE： To explore the effects of folate and choline on human DNA mismatch repair genes h MLH1,h MSH2 expressions in human colonic adenocarcinoma cells. METHODS：Modified RPMI-1640 with the combinations of 12 μmol/L choline chlorine（CC） and 15,30,120 nmol/L of folic acid（FA） or 5-methyltetrahydrofolate（5-Me THF）,FA 120 nmol/L and CC（1.5,3 μmol/L） were set as the intervening culture medium. COLO205 cells were cultured for 20 days. The transcription levels of h MLH1 and h MSH2 were analyzed by real-time fluorescence quantitative PCR. RESULTS：Transcription levels of h MLH1 and h MSH2 were significantly negatively correlated significantly with the concentrations of FA,5-Me THF or CC in tested cells（P〈0.01）. 5-Me THF was more effective on h MLH1 and h MSH2 transcription regulation than same concentration of FA at 30 and 120 nmol/L（P〈0.01 or 0.05）. CONCLUSION：We concluded that FA,5-Me THF and CC deficiency up-regulated the expressions of h MLH1 and h MSH2. This may be the cellular response to DNA damage or abnormal methylation induced by folate and choline deficiency.
出处
《癌变．畸变．突变》
CAS
CSCD
2015年第3期197-201,206,共6页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
国家自然科学基金(31260268)
联合基因生物医药有限公司合作项目
