Benzopyrene disrupts cell growth dynamics and DNA methylation in breast cancer cells
Bibliographic record
Abstract
1630 Exposure to environmental carcinogens and unhealthy lifestyle choices can contribute to incidence of breast cancer. Benzo(a)pyrene (BaP) is one such environmental carcinogen present in automobile exhaust, industrial effluent and cigarette smoke. The primary carcinogenic effects of BaP are attributed to covalent DNA modifications and the deregulation of gene expression. Furthermore, disruptions in DNA methylation represent an additional, but poorly-understood mechanism of BaP-induced carcinogenesis. Changes in normal DNA methylation patterns that ensure proper gene expression and chromosomal stability can result in deregulated gene expression and a loss of genomic integrity. However, the specific roles of environmental contaminants as contributors to breast tumourigenesis are poorly understood. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in various breast cancer cell lines. Cells were exposed to BaP in a time and concentration dependent manner and we evaluated the effects of BaP-exposure on cell proliferation and cell cycle, as well as gene-specific and global changes in DNA methylation. Our data show drastic differences in BaP-induced proliferative and cell cycle responses across these breast cancer cell lines. Specifically, we observed time and BaP concentration dependent loss of proliferation, S phase and G2M accumulation, and apoptosis in p53 positive MCF-7 and T47-D, (but not p53 negative HCC1806 and MDA MB231 cells). Furthermore, we observed increases in both p53 and p21 protein levels in BaP treated cells, while pretreatment with the p53-specific inhibitor pifithrin led to decreases in p53 and p21 levels and increase in proliferation. We also assessed DNA methylation dynamics using the methylation fingerprinting technique called amplification of intermethylated sites (AIMS), and we performed sequence analysis of differentially methylated DNA. Each cell line showed changes in global DNA methylation levels using the methyl acceptor assay (MAA), as well as gene-specific hypo- and hypermethylation events. Furthermore, we identified specific BaP-induced hypomethylation events in genomic repeats. Our data confirm altered DNA methylation patterns as a consequence of benzopyrene treatment and reinforce the link between environmental exposures, DNA methylation and breast cancer. (Funded by the Canadian Breast Cancer Research Alliance).
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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) | 0.000 | 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) | 0.002 | 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".