Relationship of intracellular glutathione concentrations with the cytotoxicity of cisplatin, acetaminophen and arsenic in tumor cell lines
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 46, 2005 1485 Intracellular glutathione (GSHi) is one of the molecules considered to be a leading candidate involved in the detoxification of many chemicals including cisplatin (DDP), acetaminophen (ACT) and arsenic compounds (Olson, Poisoning & Drug Overdose , McGraw-Hill, 2004). Higher GSHi levels have been shown in cell lines that exhibit resistance to cisplatin (DDP) as well as the other platinum compounds (Fokkema E, et al. , Biochem Pharmacol ., 2002). However, we have previously shown that tumor cells’ GSHi levels during the exposure to cytotoxic agents are not as important as kinetics of GSHi during and after the end of exposure. To investigate the importance of GSHi in the prediction of resistance to cytotoxic agents, we have selected four different tumor cell lines: hepatic HepG2, lung A549, ovary SKOV3 and kidney LLC-PK1. IC50 was calculated using clonogenic assay after 1 hour exposure of these cell lines to different agents. GSHi was measured before, during and after exposure of each cell line to different agents of DDP, ACT and As2O3 (As) up to 48 hours post-exposure. As is ranked in [table][1] below, different cell lines have shown different cytotoxicity patterns (average of IC50s in brackets, SDs are deleted to save space) in respect to GSHi level (average of the percentage of change compare to baseline in brackets, SDs are deleted to save space) after 1 hour exposure to these agents. As indicated in the table, the GSHi levels in two cell lines (ie, HepG2 and LLC-PK1) were decreasing during the exposure to the three agents. However, the GSHi levels at the end of exposure to the three agents with the other two cell lines (ie A549 & SKOV3) were significantly higher than the baseline. Only two cell lines of LLC-PK1 (r2=1 and p=0.028) and HepG2 (r2=0.98 and p=0.085) have shown a good correlation of GSHi with IC50s for different agents. Experiments using GSH depleted cells and intracellular pharmacokinetics of GSHi are on going and these results will be presented at the congress. In conclusion, there is no consistent pattern of GSHi changes between different cell lines upon exposure to cisplatin, acetaminophen or As2O3 between these four cell lines. ![Figure][2] [1]: #F1 [2]: pending:yes
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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".