The Effects of Methotrexate on Drosophila Development, Female Fecundity, and Gene Expression
Bibliographic record
Abstract
Methotrexate (MTX), a synthetic folate analog, is a tight-binding inhibitor of dihydrofolate reductase (DHFR), a key enzyme for the biosynthesis of purines, thymidylate, and several amino acids. As a consequence, MTX decreases titres of reduced folates, interferes with DNA synthesis, and results in the arrest of rapidly proliferating cells, making it a drug of choice for the treatment of a variety of cancers and auto-immune disorders. MTX is also a known teratogen in all higher animals tested, but there is little information about the effects of this drug on invertebrates. Here we show that MTX has little effect on the survival of Drosophila melanogaster adult flies, but severely diminishes female fecundity. Reduced oviposition, coupled with aberrant egg morphologies, resulted in near sterility of MTX-treated females. Rare surviving progeny showed developmental abnormalities including larval tumors, and bristle, wing, eye, and leg defects. To determine if these phenotypes could be attributed solely to DHFR inhibition, microarray analysis was undertaken and included MTX-treated females, ovaries, and cell line samples. Genes encoding transcripts that were perturbed by the drug were verified using quantitative real-time RT-PCR. Many of these genes were involved in cell cycle regulation, signal transduction, transport, defense response, transcription, or various aspects of metabolism. These studies show that MTX treatment has multiple targets and, in addition, provides a new invertebrate model for the study of teratogenesis.
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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".