Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model
Why this work is in the frame
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Bibliographic record
Abstract
Folate is an essential co-factor in the remethylation of homocysteine to methionine, thereby ensuring the supply of S-adenosylmethionine, the methyl group donor for most biological methylations, including that of DNA. Aberrant patterns and dysregulation of DNA methylation are consistent events in carcinogenesis and hence, DNA methylation is considered to be mechanistically related to the development of cancer. Folate deficiency appears to increase the risk of several malignancies, and aberrant DNA methylation has been considered to be a leading mechanism by which folate deficiency enhances carcinogenesis. Although diets deficient in methyl group donors (choline, folate, methionine and vitamin B12) have been consistently observed to induce DNA hypomethylation, the effect of an isolated folate deficiency on DNA methylation remains highly controversial and unresolved. Whether or not isolated folate deficiency can modulate DNA methylation is an important issue because it would establish a mechanistic link between folate deficiency and cancer. We examined the effects of isolated folate deficiency on methionine cycle intermediates, genomic and site-specific DNA methylation and DNA methyltransferase in an in vitro model of folate deficiency, using untransformed NIH/3T3 and CHO-K1 cells, and human HCT116 and Caco-2 colon cancer cells. Our data demonstrate that the effect of folate deficiency on the methionine cycle pathway and DNA methylation in these cells is highly complex and appears to depend on the cell type and stage of transformation, and may be gene and site-specific. The direction of changes of methionine cycle intermediates in response to folate deficiency is not uniformly consistent with the known biochemical effect of folate on the methionine cycle pathway. Moreover, the effect of folate deficiency on DNA methylation appears to be mediated by both methionine cycle intermediate-dependent and independent pathways.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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 it