Abstract
Intake of folate (vitamin B9) is strongly inversely linked with human cancer risk, particularly colon cancer. 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 colon cancer. Folate acts in normal cellular metabolism to maintain genomic stability through the provision of nucleotides for DNA replication and DNA repair and by regulating DNA methylation and gene expression. Folate deficiency can accelerate carcinogenesis by inducing misincorporation of uracil into DNA, by increasing DNA strand breakage, by inhibiting DNA base excision repair capacity and by inducing DNA hypomethylation and consequently 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 repair 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. It highlights an adaptation of the SCGE comet assay for measuring genome-wide and gene-specific DNA methylation in human cells and colon tissue.
Original language | English |
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Pages (from-to) | 73-80 |
Number of pages | 8 |
Journal | Mutation Research - Genetic Toxicology and Environmental Mutagenesis |
Volume | 843 |
Early online date | 5 Sept 2018 |
DOIs | |
Publication status | Published - Jul 2019 |
Bibliographical note
Acknowledgments: This work was supported by Tenovus Scotland and The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS). The authors are grateful to the COST Action CA15132, ‘hCOMET’ for funding a STSM to support the development of the methylation-sensitive comet assay and to Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, for funding Dr Elena Lendoiro her postdoctoral fellowship (ED481B2016/103-0).Keywords
- Colon
- Comet assay
- DNA methylation
- Folate
- Genomic stability
- Single cell gel electrophoresis
- Uracil