Dose–response mutation and spectrum analyses reveal similar responses at two microsatellite loci in benzo(a)pyrene-exposed mouse spermatogonia
Bibliographic record
Abstract
Identifying chemical exposures that can cause germline mutations is important as these mutations can be inherited, impacting both individual and population health. However, germline mutations are extremely rare and difficult to detect. Chemically induced germline mutations can be detected through analysis of highly unstable tandem repeat DNA. We recently developed a single-molecule PCR (SM-PCR) approach to quantify mutations at a mouse microsatellite locus (Mm2.2.1) in sperm for such purposes. In this study, we refine this approach through the combined analysis of mouse microsatellites Mm2.2.1 and Mm19.2.3. Mice were exposed to 0, 25, 50 or 100 mg/kg/day benzo(a)pyrene (BaP) by oral gavage for 28 days and sperm sampled 42 days after the end of exposure to measure effects on dividing spermatogonia. DNA was diluted to a single genome per PCR well for amplification of microsatellites in singleplex and multiplex reactions, and alleles were sized to identify mutations using capillary electrophoresis. Analysis of ~300-500 molecules per animal at both microsatellite loci, when tested individually, showed a ~2-fold increase in mutations relative to the controls at both the 50 and 100 mg/kg/day BaP doses. Multiplex SM-PCR revealed similar increases in mutation frequencies in both microsatellites. Comparison with results from a previous lacZ mutation assay conducted on the same mice revealed that although microsatellite mutations are a sensitive endpoint for detecting changes in mutation frequencies at lower doses, they appear to be saturable and thus have a reduced dynamic range. These results confirm that BaP is a male germ cell mutagen that broadly impacts tandem repeat DNA. Likewise, addition of a second hypervariable microsatellite increases the sensitivity of this assay.
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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".