Genotoxicity of Several Polybrominated Diphenyl Ethers (PBDEs) and Hydroxylated PBDEs, and Their Mechanisms of Toxicity
Bibliographic record
Abstract
Polybrominated diphenyl ethers (PBDEs) have been extensively utilized as flame retardants, and recently there has been concern about potential adverse effects in humans and wildlife. Their hydroxylated analogs (OH-BDEs) have received increasing attention due to their potential for endocrine and neurological toxicities. However, the potentials and mechanisms of genotoxicity of these brominated compounds have scarcely been investigated. In the present study, genotoxicity of tetra-BDEs, penta BDE, octa-BDE, deca-BDE, and tetra-OH-BDEs were investigated by use of chicken DT40 cell lines including wild-type cells and a panel of mutant cell lines deficient in DNA repair pathways. Tetra-BDEs have greater genotoxic potential than do the other BDEs tested. OH-tetra-BDEs were more genotoxic than tetra-BDEs. DT40 cells, deficient in base excision repair (Polβ(-/-)) and translesion DNA synthesis (REV3(-/-)) pathways, were hypersensitive to the genotoxic effects of tetra-BDEs and OH-tetra-BDEs. The observation of chromosomal aberrations and gamma-H2AX assay confirmed that the studied brominated compounds caused double strand breaks. Pretreatment with N-acetyl-l-cysteine (NAC) significantly rescued the Polβ(-/-) and REV3(-/-) mutants, which is consistent with the hypothesis that PBDEs and OH-BDEs cause DNA damage mediated through reactive oxygen species (ROS). Some tetra-BDEs and OH-tetra-BDEs caused base damage through ROS leading to replication blockage and subsequent chromosomal breaks.
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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) | 0.000 | 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".