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

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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)73-80
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume843
Early online date5 Sep 2018
DOIs
Publication statusPublished - Jul 2019

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Comet Assay
Environmental Monitoring
Genomic Instability
Folic Acid
Colonic Neoplasms
DNA Repair
DNA
Uracil
DNA Methylation
Gene Expression
In Vitro Techniques
DNA Replication
Case-Control Studies
Rodentia
Colon
Carcinogenesis
Nucleotides
Genome

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

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. (Corresponding Author).

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 843, 07.2019, p. 73-80.

Research output: Contribution to journalArticle

Catala, Gema Nadal ; Bestwick, Charles S. ; Russell, Wendy R. ; Tortora, Katia ; Giovannelli, Lisa ; Moyer, Mary Pat ; Lendoiro, Elena ; Duthie, Susan J. / 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. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2019 ; Vol. 843. pp. 73-80.
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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.",
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