Abstract 942: Effects of maternal and postnatal folic acid supplementation on genomic DNA methylation in the mammary glands in a chemical rat model of mammary tumorigenesis
Bibliographic record
Abstract
Abstract Background: Widespread loss of genomic DNA methylation is an early and consistent epigenetic event in cancer development including breast carcinogenesis. Folate, an essential co-factor in the transfer of one-carbon units, has been shown to modulate both cancer risk and genomic DNA methylation. We recently observed that folic acid (FA) supplementation provided in utero and in early postnatal life significantly increased risk of mammary tumors in the offspring in the dimethylbenzanthracene (DMBA) rat model. To determine a potential underlying mechanism of FA-mediated mammary tumor development, we investigated the association between global DNA methylation, DNA methyltransferase (DNMT) activity, FA supplementation, and mammary tumor status in the offspring. Methods: Female Sprague-Dawley rats were placed on a control diet (2 mg FA/kg diet) or a supplemented (5 mg) diet for 3 weeks prior to breeding and throughout pregnancy and lactation. At weaning, female pups were randomized to the control or supplemented diet. At 7 weeks of age, all pups received a single intragastric dose (5 mg) of DMBA to induce mammary tumors. At 28 weeks of age, plasma, mammary gland and liver folate and plasma homocysteine concentrations were determined and mammary tumors were enumerated and histologically confirmed. Genomic DNA methylation and DNMT activity were determined in non-neoplastic mammary glands. Results: Plasma, liver, and mammary folate and homocysteine concentrations accurately reflected dietary FA levels at weaning and 28 weeks of age (p<0.05). A significant interaction was observed between genomic DNA methylation and mammary adenocarcinoma status in the offspring (p<0.001), indicating that among tumor-free offspring, genomic DNA methylation was significantly decreased by maternal FA supplementation. In addition, in offspring bearing at least one adenocarcinoma, genomic DNA methylation was significantly decreased regardless of dietary FA intervention. Postweaning FA supplementation independently decreased DNMT activity in the offspring (p=0.05). Conclusions: Our data suggest that decreased genomic DNA methylation and DNMT activity associated with maternal and postweaning FA supplementation might be a mechanism by which maternal and postweaning FA supplementation increased mammary tumorigenesis in the offspring. Given the drastic increase in FA intake among women of childbearing age in North America, future studies are need to determine whether or not FA supplementation increases the risk of breast cancer through epigenetic mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 942.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".