Administration of Diethylnitrosamine in the Immediate Postnatal Period Coupled with Exposure to a Choline Deficient Diet Accelerates Hepatocarcinogenesis in the Rat
Bibliographic record
Abstract
The objectives of this study were to determine if the combination of: i. neonatal administration of diethylnitrosamine and ii. subsequent feeding of a choline deficient diet could accelerate hepatic premalignancy in the rat. The presence and size of premalignant nodules and the activity of the liver cancer enzyme marker g-glutamyltranspeptidase (gGT) were used as indicators of hepatic premalignancy. Three day old Fisher 344 rats were administered sc, saline or diethylnitrosamine (DENA): 100 mg/Kg. These were divided into choline sufficient (CS) and choline deficient (CD) groups with diets introduced to dams. On postnatal day 21 rats were weaned onto CS or CD diets. Rats in choline sufficient saline-injected (CS), choline sufficient DENA-injected (CS+DENA), choline deficient saline-injected (CD) and choline deficient DENA-injected (CD+DENA) groups were assessed on day 86. Livers of CS and CS+DENA rats were normal in appearance. Livers of CD rats were paler; those of CD+DENA rats contained visible, large, tan liver nodules. Identical results were observed in both sexes. Liver gGT activity was low and comparable in rats of CS and CS+DENA groups. Relative to liver homogenate gGT activity in the CS group, liver homogenate gGT was increased in the CD group: 14.5 fold in males and 18 fold in females; and further increased in the CD+DENA group: 78 fold in males and 54 fold in females. Plasma g-glutamyltranspeptidase exhibited the same trends as liver. The CD+DENA group demonstrated the largest increase in activity: 158 fold in males; 199 fold in females over that in the CS group. Male and female rats belonging to CS and CS+DENA groups were euthyroid; those in CD and CD+DENA groups were hypothyroid. Compared to hormone levels in the CS group, in the CD group, decreases in T3 were: 27% in males and 13% in females; decreases in T4 were: 29% in males and 5.6% in females. Compared to hormone levels in the CS groups, in the CD+DENA groups, decreases in T3 were: 25% in males and 18% in males; decreases in T4 were: 31% in males and 25% in females. Plasma glucose levels were comparable in rats of CS and CS+DENA groups. Relative to these levels, plasma glucose levels in rats of CD and CD+DENA groups were decreased 30% in males and females. Plasma transaminase levels were low and comparable in all groups. The protocol developed accelerated hepatocarcinogenesis in the Fischer 344 rat. In CD+DENA male and female rats, it produced, in 86 days, visible, large hyperplastic lesions displaying high levels of gGT and high levels of plasma gGT that are consistent with being at a well developed advanced premalignant stage of hepatocarcinogenesis without any sign of toxicity.
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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".