Abstract 2550: Expanded simple tandem repeat (ESTR) mutations in offspring of benzo(a)pyrene exposed DNA repair deficient male mice
Bibliographic record
Abstract
Abstract Germ line mutations can be transmitted to the offspring and may thus affect an infinite number of generations thereafter. To study germ line mutations, expanded simple tandem repeats (ESTR) can be used as a sensitive tool, because they are known to be highly unstable and therefore exhibit high mutation rates. This facilitates the assessment of germ line mutations in a relatively small number of offspring following exposures that may pose a genetic risk to the germ line. We used two ESTR loci Ms6-hm and Hm-2 in families of benzo(a)pyrene (BaP) exposed and unexposed male mice, proficient or deficient for global genome repair (Xpc-/-). Male mice (C57BL/6) were exposed to BaP during 6 weeks (13 mg/kg bw, 3 times per week) and were crossed with female mice (Balb/C) 6 weeks after the last exposure to obtain offspring and to ensure the analysis of mutations originating from spermatogonial stem cells. The overall ESTR mutation rate at both ESTR loci, irrespective of the DNA repair capacity, was higher in offspring of benzo(a)pyrene exposed mice than in control mice (9.4% vs. 4.5%, P=0.054). This effect was predominantly seen in BaP exposed DNA repair deficient Xpc-/- mice; mutation frequencies were 12.5% in the exposed group (12 out of 96 offspring carried a mutant allele) and 3.4% in the unexposed group (3 out of 87), respectively (P=0.024). In DNA repair proficient mice, BaP was unable to increase the mutation frequency transmitted to the offspring (5.8% vs. 5.5% for offspring of exposed and unexposed fathers). These results indicate that analysis of tandem repetitive sequences is a sensitive method for the detection of germline mutations transmitted to the offspring and that the environmental mutagen BaP is able to induce germ line mutations in DNA repair deficient mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2550. doi:1538-7445.AM2012-2550
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 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) | 0.006 | 0.001 |
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".