Effect Of Folic Acid On Telomere Length And Chromosomal Instability In Human BJ And A375 Cell Lines

Telomeres are nucleoprotein structure located at the ends of eukaryotic chromosomes. Functionally intact and structural integrity telomeres are critical for maintaining chromosome stability; they protect chromosomes from end-to-end fusions and chromosome rearrangement. Telomeres shorten progressively with cell division in the absent of telomere maintenance mechanism, and telomere length is becoming an important biomarker for genome stability and cell senescence. Telomere length is maintained by telomerase or alternative lengthening of telomeres(ALT) mechanism in cells. Folate is an important micronutrient in the one-carbon metabolism network, which is essential for DNA synthesis, repair and methylation. We hypothesized that DNA damage or chromosomal instability(CIN) caused by folate deficiency would be related to telomere length changes. In our study, human normal fiber cell line BJ and malignant melanoma cell line A375 were cultured in medium containing different concentrations of folic acid(FA)(30~3000 nmol/L) for 21 days to test the absolute telomere length(aTL) using real time-quantitative PCR(RT-qPCR), chromosome instability were evaluated by cytokinesis-block micronucleus cytome assay(CBMN-Cyt).The results showed that:(1) BJ cells in FA 30 nmol/L, telomere length presented abnormal growth or shortened with the extension of intervention time, CIN was significantly increased(P < 0.05), in FA 100 ~ 300 nmol/L, telomere length appeared positive correlation with FA concentrations, in FA 1000 nmol/L, telomere length and CIN remained stability.(2) A375 cells in FA 30 ~ 3000 nmol/L, telomere length showed a trend of growth longer in 15 day then shorten in 21 day(P < 0.05), in FA 30 nmol/L, CIN were significantly higher than control(P = 0.013).In summary, this study indicated that telomere length of BJ cells was associated with FA concentrations. Folate deficiency in normal cells would induce abnormal telomere length and chromosomal instability. Changes in telomere length and chromosomal stability of A375 cells did not significantly depend on folic acid, which suggested that different transformation states of cells would have different response mechanisms on folate deficiency.