Radiation-induced molecular changes in rat mammary tissue: Possible implications for radiation-induced carcinogenesis
Bibliographic record
Abstract
PURPOSE: Ionizing radiation is a potent mammary gland carcinogen, yet the exact molecular etiology of radiation-induced breast cancer remains unknown. MATERIALS AND METHODS: Our study utilized a rat model of breast carcinogenesis to analyse the molecular and epigenetic changes induced in mammary gland tissue upon exposure to ionizing radiation (IR). Using a methylation-sensitive cytosine extension assay we studied the IR-induced changes in DNA methylation. In parallel, we analysed the expression of proteins involved in DNA methylation, DNA repair and cell proliferation control. Molecular changes were related to cellular proliferation and apoptosis. RESULTS: We found that IR led to a loss of genomic cytosine methylation in the exposed mammary tissue. Global DNA hypomethylation was paralleled by reduction in the levels of maintenance (DNMT1) and de novo (DNMT3a and 3b) DNA methyltransferases and methyl-binding protein MeCP2. The observed DNA hypomethylation was linked, at least in part, to activation of DNA repair processes. Concurrently, we observed increased levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated AKT kinase (p-AKT), cyclin D1 and proliferating cells nuclear antigen (PCNA) proteins, suggesting IR alters intra-cellular signaling and cell cycle control mechanisms in mammary tissue. We also noted a significant induction of apoptosis in the exposed tissue 6 hours after irradiation. The observed apoptosis levels were paralleled by the slight elevation of cellular proliferation. CONCLUSIONS: We have demonstrated that a single exposure to 5 Gy of X rays leads to noticeable epigenetic changes in the rat mammary gland that occurred in the context of activation of DNA damage repair and alterations in the pro-survival growth-stimulatory cellular signaling pathways. The possible cellular repercussions of the observed changes in relationship to breast carcinogenesis are discussed.
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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 | 0.000 | 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 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".