Niacin Deficiency Alters p53 Expression and Impairs Etoposide-Induced Cell Cycle Arrest and Apoptosis in Rat Bone Marrow Cells
Bibliographic record
Abstract
One focus of chemoprevention research is the interaction of nutrients with specific molecular targets associated with the maintenance of genomic stability. This study tested the impact of dietary niacin status on bone marrow NAD+ and poly(ADP-ribose) (pADPr) levels, p53 expression, and etoposide (ETO)-induced apoptosis and cell cycle arrest. After 3 wk on niacin-deficient (ND), pair-fed niacin-replete (PF), or nicotinic acid-supplemented (4 g/kg diet) (NA) diets, Long-Evans rats were gavaged with ETO (25 mg/kg) or vehicle. ND and NA diets caused a 72% decrease and a 240% increase in bone marrow NAD+, respectively. Basal and ETO-induced pADPr levels differed dramatically among ND, PF, and NA diets (undetectable, 42 and 216 fmol/million cells, respectively; basal and undetectable, 119 and 484 fmol/million cells, respectively, following ETO). ND diet alone caused overexpression of two distinct isoforms of p53. Levels of p53 in PF and NA marrow increased in response to ETO treatment, but this did not occur in ND bone marrow. Quantitative polymerase chain reaction of regular and alternative spliced variants of p53 mRNA revealed that niacin deficiency actually decreased both forms of p53 message, implicating protein stability in the accumulation of p53 in ND marrow. ETO-induced apoptosis (TUNEL) was suppressed during niacin deficiency and enhanced by supplementation. G1 arrest was also impaired in ND bone marrow relative to PF and NA. Despite a poor G1 arrest, p21waf1 was overexpressed in the ND bone marrow and dramatically induced following ETO treatment. In conclusion, dietary niacin deficiency causes changes in NAD+ and pADPr metabolism, alters p53 expression, and impairs cellular responses to DNA damage.
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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".