Attempted Modulation of Disulfide Antitumor Activity in Balb/c Mice through Glutathione Depletion
Bibliographic record
Abstract
We investigated the effects of buthionine sulfoximine (BSO)-mediated glutathione (GSH) depletion on the antitumor activity in Balb/c mice produced by four disulfide derivatives of 6-TG and 6-MP. Initial studies indicated that 14 h after BSO (5 mmol/kg) injections, tumor GSH levels were maximally depleted, while normal tissue GSH levels had returned to near control levels. Tumor growth delays and growth rates were compared for groups of animals receiving disulfides I–IV with and without BSO administration 14 h previous. Treatments with BSO alone produced no delay or growth rate differences from the control. Compounds II or III administered in the presence and absence of BSO also produced no delay or growth rate differences from control. Compound I (10 mg/kg) alone showed a delay of 5.2 days and a growth rate significantly slower than that of control (p = 0.05). In combination with BSO the effects were not enhanced. Compound IV (50 mg/kg) also produced delays in 2 separate trials (3.1 and 4.8 days) and significantly slower growth rates on each occasion compared to the control (p = 0.05). The growth rates were not significantly lowered in the presence of BSO. Administration of two doses of IV, 4 days apart, produced a delay (4.9 days) similar to that seen with a single dose. It produced 2 cures and was also more toxic, causing 3 deaths. Two doses of IV in combination with BSO pretreatment had a greater delay (16.0 days) and a significantly longer growth rate (p = 0.05) than two doses of IV alone. This treatment produced 1 cure, but also increased the number of deaths to 5/8. 6-TG (50 mg/kg) produced a delay of 11.8 days which was not enhanced with BSO. If compared to that of IV, on an equimolar ratio the delay produced by 6-TG was equivalent. BSO pretreatment, in general, was more toxic than drug alone and provided enhancement of antitumor activity only with the double dose of compound IV (50 mg/kg).
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 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".