請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/62043
標題: Folate restriction and methylenetetrahydrofolate reductase 677T polymorphism decreases adoMet synthesis via folate-dependent remethylation in human-transformed lymphoblasts
作者: Chiang, E.P.
蔣恩沛
Wang, Y.C.
Tang, F.Y.
關鍵字: methylenetetrahydrofolate reductase
folate
DNA synthesis
DNA
methylation
S-adenosyl methionine
acute lymphocytic-leukemia
non-hodgkins-lymphoma
mthfr polymorphisms
c677t polymorphism
dna methylation
dietary-folate
promoter
hypermethylation
malignant-lymphoma
cancer-cells
risk
期刊/報告no:: Leukemia, Volume 21, Issue 4, Page(s) 651-658.
摘要: The homozygous mutation (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene reduces enzyme activity and alters cellular folate composition. Previous epidemiological studies reported a potential protective effect of MTHFR677C -> T against acute lymphocytic leukemia and malignant lymphoma, but the mechanism remains to be determined. We investigated the biochemical impacts of MTHFR677C -> T on cellular S-adenosyl methionine (adoMet) synthesis, global DNA methylation, and de novo purine synthesis, all of which are potential regulatory pathways involved in tumorigenesis. Metabolic fluxes of homocysteine remethylation and de novo purine synthesis were compared between Epstein - Barr virus-transformed lymphoblasts expressing MTHFR 677C and MTHFR 677T using stable isotopic tracers and GCMS. MTHFR TT genotype significantly reduced folate-dependent remethylation under folate restriction, reflecting limited methylated folates under folate restriction. Data also suggested increased formylated folate pool and increased purine synthesis when folate is adequate. The impacts of MTHFR 677T polymorphism appeared closely related to folate status, and such alterations may modulate metabolic pathways involved in cancer onset/ progression. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in hematological malignancies. These transformed cells are potential models for studying the consequences of human genetic variation and cancer pathogenesis.
URI: http://hdl.handle.net/11455/62043
ISSN: 0887-6924
文章連結: http://dx.doi.org/10.1038/sj.leu.2404575
顯示於類別:食品暨應用生物科技學系

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