Abstract: BACKGROUND ＆ AIM: Folic acid (FA) is a key factor that is involved in DNA methylation and DNA synthesis. Methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme which determines the balance between the above two processes. Riboflavin(RF) is the precursor of flavin adenine dinucleotide (FAD) which is the coenzyme of MTHFR, consequently, low concentration of RF may affect MTHFR activity. MATERIALS AND METHODS: Cytokinesis_block micronucleus assay (CBMN) was employed to assess the effects of different combinations of FA(20 and 200 nmol/L, i.e. LF and HF) and RF (1 and 500 nmol/L, i.e. LR and HR) and MTHFR A1298C polymorphism on genomic stability of 9_day old cultured human lymphocytes. RESULTS: The result showed that the genetic damage was significantly higher in LFHR groups regardless of the genotypes(P<0.01).The optimal levels of genomic stability were identified in all HFLR groups. The frequencies of MNed BNC, NPB and BUD in HF groups were 46.5％,22％ and 42.3％, respectively, of those in LF. These biomarkers levels were 6.3％－12.4％ lower in LR groups than in HR groups. FA accounted for 91.61％，73.72％ and 78.07％ for MNed BNC,NPB and BUD respectively. RF and MTHFR A1298C polymorphism did contribute to the variations of the above indexes but the impact was relatively trivial compared with that of FA. No interactions among these three factors that affected the genomic stability were found. CONCLUSION:All of FA,RF and MTHFR A1298C polymorphism could affect genomic stability, with FA being the dominant factor in our system.

Key words: folic acid, riboflavin, MTHFR polymorphism, cytokinesis_block micronucleus assay, genomic stability