Abstract: BACKGROUND ＆ AIM：Methionine synthase(MS) catalyzes the tetrahydrofolate transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine (Met) and tetrahydrofolate. Met is the precursor of S-adenosylmethionine, which is a crucial methyl group donor in DNA methylation. Vitamin B12 (B12) is a co-factor of MS and plays an important role in folate metabolism. This experiment aimed to evaluate the genotoxic effects of Met and B12 deficiency in human lymphoblast cell line carrying BRCA1 mutation. MATERIAL AND METHODS: Lymphoblast cells were cultured under 10 different combined of vitamin B12 (100,300,600,800,1 200 pmol/L) and methionine (15 μmol/L and 50 μmol/L) concentration medium for 9 days. Routine RPMI 1640 medium was set as the control. The frequencies of micronucleated binucleated cell (MNBN) were evaluated by cytokinesis-block micronucleus assay(CBMN). RESULTS: The frequencies of MNBN were significantly higher in 15 μmol/L of Met combined with all concentrations of B12 than that of 50 μmol/L of Met with all B12 concentrations(P<0.05). The frequencies of MNBN were makedly reduced when 50 μmol/L of Met and 600 pmol/L of B12 were used. CONCLUSION: A significant inhibitory effect of MNBN was found at 600 pmol /L of B12. There were no significant differences found among 600,800,1 200 pmol/L of B12 and RPMI1640 medium groups. We concluded that 50 μmol/L of Met and 600 pmol/L of B12 formed an optimal combination for stabilizing the genome of the test cell line. This preliminary investigation suggested that Met and B12 deficiency caused genomic instability. One might consider supplying adequate amounts of Met and B12 to maintain genome stability.

Key words: Vitamin B12, methionine, cytokinesis-block micronucleus assay, micronucleated binucleated cell