The Impacts Of Folic Acid, Riboflavin Deficiency And MTHFR Polymophism On Genome Stability In Human Lymphocytes

Folic acid (FA) is an important micronutrient in human body. It is required for the synthesis of dTMP from dUMP. At the same time, FA is required for the synthesis of S-adenosyl methionine via a series of metablism, the common methyl donor required for the maintenance of methylation patterns in DNA that determine gene expression and DNA conformation and that assure some high methylation on some chromosomes that is greatly important to normally separate during mitotic division. In FA metablism, Methylenetetrahydrofolate reductase (MTHFR) acts as a critical juncture in folate metabolism by catalyzing the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-methyl THF), thereby committing folate metabolites to homocysteine remethylation and synthesis of the primary methyl donor for cellular methylation reactions, S-adenosylmethionine (SAM).The two common polymorphisms in the MTHFR gene, 677 C→T and 1298 A→C, have been implicated as risk factors for several cancers. Homozygosity for the 677 C→T polymorphism and compound heterozygosity for 677 C→T and 1298 A→C polymorphisms both reduce enzyme activity. Riboflavin is precursor of flavin adenine dinucleotide (FAD) and FAD is cofactor of MTHFR. So folic acid and riboflavin deficiency and methylenetetrahydrofolate reductase gene polymorphisms not only lead to point mutation but may also result in the generation of single- and double-stranded DNA breaks, chromosome breakage and of the activation of proto-oncogene.We employ Multiplex polymerase chain reaction-Restriction fragmentl ength polymorphism to identify MTHFR 677 C→T and 1298 A→C polymor phisms in breast cancer cases and healthy subjects. We also study the effect of the cytotoxicity and genotoxicity in Human lymphocyte in folic acid and ribofla vin deficiency by the cytokinesis-block micronucleus assay from which we obtai n a comprehensive information of the cytotoxicity and genotoxicity.The experime nt aimed to evaluate the effect of FA, riboflavin and MTHFR polymorphisms o...