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.

Catala, Gema Nadal; Bestwick, Charles S.; Russell, Wendy R.; Tortora, Katia; Giovannelli, Lisa; Moyer, Mary Pat; Lendoiro, Elena; Duthie, Susan J.

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.

Citation

CATALA, G.N., BESTWICK, C.S., RUSSELL, W.R., TORTORA, K., GIOVANNELLI, L., MOYER, M.P., LENDOIRO, E. and DUTHIE, S.J. 2019. 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. Mutation research: genetic toxicology and environmental mutagenesis [online], 843, pages 73-80. Available from: https://doi.org/10.1016/j.mrgentox.2018.08.012

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2018
• Online Publication Date: Sep 5, 2018
• Publication Date: Jul 31, 2019
• Deposit Date: Sep 6, 2018
• Publicly Available Date: Sep 6, 2019
• Journal: Mutation Research - Genetic Toxicology and Environmental Mutagenesis
• Print ISSN: 1383-5718
• Electronic ISSN: 1879-3592
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 843
• Pages: 73-80
• DOI: https://doi.org/10.1016/j.mrgentox.2018.08.012
• Keywords: Single cell gel electrophoresis; Comet assay; Folate; Genomic stability; Colon; Uracil; DNA methylation
• Public URL: http://hdl.handle.net/10059/3119