Methylenetetrahydrofolate reductase deficiency and low dietary folate reduce tumorigenesis in <i>Apc<sup>min/+</sup> </i> mice
Bibliographic record
Abstract
BACKGROUND: Clinical studies suggest that mild methylenetetrahydrofolate reductase (MTHFR) deficiency and high dietary folate may reduce the risk for colorectal cancer. There is concern, however, that high folate intake (a consequence of food fortification) may enhance tumour growth in individuals with pre-existing tumours or genetic predisposition to tumorigenesis. AIM: To determine if Mthfr deficiency and low dietary folate influence tumorigenesis in mice genetically predisposed to form numerous intestinal adenomas (Apc(min/+)). METHODS: Male Apc(min/+) mice were mated with Mthfr(+/-) and/or Mthfr(+/+) females. Diets with variable folate content were administered either pre-natally or at weaning; tumours were counted in offspring at 10 weeks of age. Plasma homocysteine and levels of apoptosis, DNA methylation and nucleotide ratios (dUTP:dTTP) in normal (pre-neoplastic) intestine were measured. RESULTS: Apc(min/+) mice fed high folate diets from weaning developed more adenomas than those fed the folic acid-deficient diet (FADD) or the control diet (CD); Mthfr deficiency did not affect adenoma number. However, when the FADD and CD were administered to dams prior to conception, throughout pregnancy and continued in offspring post-weaning, Apc(min/+) offspring fed FADD developed fewer adenomas than those fed CD. Mthfr(+/-) genotype of the mother or of the offspring also reduced adenoma numbers in the Apc(min/+) offspring. Adenoma number was inversely correlated with plasma homocysteine (r = -0.49, p<0.005, intestinal dUTP/dTTP ratios (r = -0.42, p = 0.05), and levels of intestinal apoptosis (r = -0.36, p = 0.08). CONCLUSIONS: Low dietary folate and Mthfr deficiency reduce adenoma formation in mice predisposed to tumorigenesis, possibly through increased apoptosis consequent to hyperhomocysteinaemia and nucleotide imbalances.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".