Effects of<i>N</i><sup>1</sup>,<i>N</i><sup>13</sup>-Diethylnorspermine (DENSPM) and X-Radiation Treatment on Human Colorectal Tumor Clones with Varying X-Radiation and Drug Responses
Bibliographic record
Abstract
This study was designed to examine the effects of treatment with N1, N13-diethylnorspermine (DENSPM), a spermine analog, and X radiation on survival and on the polyamine and spermidine/spermine N1-acetyltransferase (SSAT) levels in closely related human colorectal tumor (HCT116) clones exhibiting a wide range of X-radiation and drug responses. After treatment with DENSPM and X radiation, clonogenic cell survival was measured. SSAT protein levels were measured by Western blot analysis and SSAT enzymatic activities by the conversion of [1-14C]acetyl-CoA into [1-14C]acetylspermidine. Polyamine [i.e. putrescine (PUT), spermine (SPM) and spermidine (SPD)] levels were measured with high-performance liquid chromatography. DENSPM enhanced the efficacy of radiation treatment in HCT116, HCT116-Clone2 (a radiation-resistant clone) and HCT116-Clone10 (a clone with similar X-radiation response as the parental HCT116 cells) but not in HCT116-CloneK (an X-radiation-sensitive but relatively drug-resistant clone). Treatment with DENSPM without X radiation caused the most significant increase in SSAT activity (approximately 22-fold) and an almost complete depletion of SPD levels in HCT116-CloneK. Our results suggest that (a) the lack of sensitization of X-radiation treatment by DENSPM in HCT116-CloneK was likely due to the prior depletion of SPD levels by DENSPM alone, (b) natural polyamine contents and/or inducibility of SSAT may be important factors influencing cellular response to combined X-radiation and DENSPM treatments, and (c) more importantly, there may be a potentially novel role for combining polyamine analogs such as DENSPM with X rays.
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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 | 0.001 | 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".