叶酸缺乏的影响,MTHFR C677T多态性自发和辐射诱导人类淋巴细胞微核。

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源P, Marcon F, Caiola年代,Cafolla, Siniscalchi E, Zijno, Crebelli R

叶酸缺乏的影响,MTHFR C677T多态性自发和辐射诱导人类淋巴细胞微核。

诱变。2006年9月21日(5):327 - 33所示。Epub 2006 9月1。

PubMed ID

16950805 (在PubMed

]

文摘

叶酸在维持基因组稳定中发挥着关键作用,提供甲基尿嘧啶转换成胸腺嘧啶和DNA甲基化。除了饮食习惯,叶酸代谢是受遗传多态性的影响。的中还原酶(MTHFR)基因C677T多态性与催化活性的降低,建议修改不同的癌症风险取决于叶酸状态。在这工作的影响叶酸缺乏对基因组稳定性和辐射敏感度研究在12个学科培养的淋巴细胞与不同的MTHFR基因型为每个基因型(4)。细胞生长9天的12、24和120 nM叶酸和分析全面微核测试加上着丝粒特性波峰疣状。在其他的实验中,细胞生长与各种叶酸浓度,与0.5 Gy的伽马射线辐照微核测试和分析。结果表明,叶酸缺乏导致在相当程度上染色体丢失和破损,无论MTHFR基因型。叶酸的作用非常显著(P < 0.001)和解释> 50%的方差的两种类型的微核。也显著增加,核质桥梁和味蕾在低叶酸供应;桥梁的增加主要是观察到TT细胞,突出的显著影响MTHFR基因型在这个生物标志物(P = 0.006)。 Folic acid concentration significantly affected radiation-induced micronuclei (P < 0.001): the increased incidence of radiation-induced micronuclei with low folic acid was mainly accounted for by carriers of the variant MTHFR allele (both homozygotes and heterozygotes), but the overall effect of genotype did not attain statistical significance. Treatment with ionizing radiations also increased the frequency of nucleoplasmic bridges. The effect of folic acid level on this end-point was modulated by the MTHFR genotype (P for interaction = 0.02), with TT cells grown at low folic acid concentration apparently resistant to the induction of radiation-induced bridges. Finally, the effect of in vitro folate deprivation on global DNA methylation was evaluated in lymphocytes of six homozygous subjects (three CC and three TT). The results obtained suggest that, under the conditions of this work, folic acid deprivation is associated with global DNA hypermethylation.

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药物靶点

药物	目标	类	生物	药理作用	行动
四氢叶酸	Methylenetetrahydrofolate还原酶	蛋白质	人类	未知的	代数余子式	细节