Abstract: OBJECTIVE: To investigate the effects of folic acid on N-methyl-N-nitro-N'-nitrosoguanidine (MNNG)-treated esophageal epithelial cells,in expression of DNMT1 activity and to provide a theoretical basis for the prevention and treatment of esophageal cancer. METHODS: Using a 3 factors and 3 levels (3×3) factorial design,esophageal epithelial cells in culture were exposed to different concentrations of folic acid (0.000,0.400,0.800 μg/mL) and MNNG (0,0.750,1.500 μg/mL) for 48,72 and 96 h. DNA methyltransferase activity was detected by ELISA;DNMT1 mRNA expression by RT-PCR;DNMT1 protein expression by Western blot method. RESULTS: Treatment of cells with different concentrations of folic acid and MNNG and in different times,at a fixed MNNG concentration and time factors,and with increasing concentrations of folic acid,the DNMT1 activity, DNMT1 mRNA and protein expression levels all gradually decreased (P<0.01). By fixing folic acid concentrations and time,and with increasing concentrations of MNNG,DNMT1 enzyme activity, DNMT1 mRNA and protein expression levels all increased (P<0.01). By fixing the MNNG and folic acid concentrations with intervention,the extension of time of DNMT1 activity,DNMT1 mRNA and protein expression levels all gradually increased (P<0.01). There were interactions between MNNG concentrations and action time,and folic acid and MNNG concentrations (P<0.01). There were significant differences between different concentrations of folic acid and different action time,between different MNNG concentrations and different time of action (P<0.05). CONCLUSION: Lower folate concentrations had a negative impact on the expression and effect of MNNG on DNMT1 activity in esophageal epithelial cells. The results suggest that folic acid played a role in promoting the occurrence of esophageal carcinoma,and had a protective effect against MNNG toxicity.

Key words: folic acid, MNNG, esophageal epithelial cells, DNA methyltransferases 1, Kazakh