Evidence map›Paper›PMID 39326632›Full record

ArticleThe Journal of nutrition2024

Excess Folic Acid Exposure Increases Uracil Misincorporation into DNA in a Tissue-Specific Manner in a Mouse Model of Reduced Methionine Synthase Expression.

Katarina E Heyden, Olga V Malysheva, Amanda J MacFarlane, Lawrence C Brody, Martha S Field

Abstract read
In one paragraph

Article in The Journal of nutrition, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Katarina E HeydenDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Olga V MalyshevaDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Amanda J MacFarlaneTexas A&M Agriculture, Food, and Nutrition Evidence Center, Fort Worth, TX, United States; Department of Nutrition, Texas A&M University, College Station, TX, United States.
Lawrence C BrodyGene and Environment Interaction Section, National Human Genome Research Institute, NIH, Bethesda, MD, United States.
Martha S FieldDivision of Nutritional Sciences, Cornell University, Ithaca, NY, United States. Electronic address: mas246@cornell.edu.

Funding

Zeiss LSM710 Confocal Microscope for Shared Imaging FacilityS10RR025502 · NCRR · CORNELL UNIVERSITY · PI WILLIAMS, REBECCA M · 2009 to 2009
$500k
NCRR NIH HHS S10 RR025502
6 · The paper itself

Abstract

backgroundFolate and vitamin B12 (B12) are cofactors in folate-mediated 1-carbon metabolism (FOCM), a metabolic network that supports synthesis of nucleotides (including thymidylate [dTMP]) and methionine. FOCM impairments such as a deficiency or imbalance of cofactors can perturb dTMP synthesis, causing uracil misincorporation into DNA.

objectiveThe purpose of this study was to determine how reduced expression of the B12-dependent enzyme methionine synthase (MTR) and excess dietary folic acid interact to affect folate distribution and markers of genome stability in mouse tissues.

methodsHeterozygous Mtr knockout mice (Mtr

resultsExposure to the HFA diet led to tissue-specific patterns of folate accumulation, with plasma, colon, kidney, and skeletal muscle exhibiting increased folate concentrations compared with control. Liver total folate did not differ. Although unmetabolized folic acid (UMFA) increased 10-fold in mouse plasma with HFA diet, UMFA accounted for <0.2% of total folate in liver and colon tissue. Exposure to HFA diet resulted in a shift in folate distribution in colon tissue with higher 5-methyl-THF and lower formyl-THF than in control mice. Mtr heterozygosity did not impact folate accumulation or distribution in any tissue. Mice on HFA diet exhibited higher uracil in genomic DNA and γH2AX foci in colon. Similar differences were not seen in liver.

conclusionsThis study demonstrates that folic acid, even when consumed at high doses, does not meaningfully accumulate in mouse tissues, although high-dose folic acid shifts folate distribution and increases uracil accumulation in genomic DNA in colon tissue.

Indexed as

5-Methyltetrahydrofolate-Homocysteine S-MethyltransferaseFolic AcidMice, KnockoutUracilAnimalsDietDNAHistonesLiverMaleMiceMice, Inbred C57BLVitamin B 125-Methyltetrahydrofolate-Homocysteine S-MethyltransferaseDNAFolic AcidHistonesUracilVitamin B 12DNAfolatemethionine synthaseunmetabolized folic acid (UMFA)vitamin B12

Identifiers

PMID39326632
PMCPMC11600115

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.