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Mutat Res. 2019 Jul;843:73-80. doi: 10.1016/j.mrgentox.2018.08.012. Epub 2018 Sep 5.

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.

Author information

1
Natural Products Group, Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
2
Department NEUROFARBA, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.
3
INCELL Corporation, San Antonio, TX, USA.
4
Department of Toxicology, Institute of Forensic Sciences, University of Santiago of Compostela, Santiago de Compostela, Spain; School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, UK.
5
Natural Products Group, Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK; School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, UK. Electronic address: s.j.duthie@rgu.ac.uk.

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.

KEYWORDS:

Colon; Comet assay; DNA methylation; Folate; Genomic stability; Single cell gel electrophoresis; Uracil

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