Folate, genomic stability and colon cancer: the use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring.

Intake of folate (vitamin B9) is strongly linked with human cancer risk, particularly colon cancer (CC). In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing CC. Folate acts in normal cellular metabolism to maintain genomic stability through the provision of nucleotides for DNA synthesis and DNA repair and by regulating DNA methylation and gene expression. Conversely, folate deficiency can accelerate carcinogenesis by inducing misincorporated uracil into DNA, by increasing DNA strand breakage, by inhibiting DNA BER repair capacity and by inducing DNA hypomethylation and consequentially aberrant gene and protein expression. Conversely, increasing folate intake may improve genomic stability. This review describes key applications of single cell gel electrophoresis (the comet assay) in assessing genomic instability (misincorporated uracil, DNA single strand breakage and DNA BER capacity) in response to folate status (deficient or supplemented) in human cells in vitro, in rodent models and in human case control and intervention studies, and highlights an adaptation of the SCGE assay for measuring genome-wide and gene-specific DNA methylation in human cells and colon tissue.