Epigenomic and Gene Expression Changes in Testicular Cells From Exposure to Phthalates
Bibliographic record
Abstract
PP-30-181 Background/Aims: Epigenetic changes disrupting the regulation of gene expression are a common process in the development of cancer. Testicular germ cell tumor (TGCT) is the most common malignancy in young males, and its incidence has been rising in recent years. Epigenetic mechanisms have been known to be associated with gene silencing in TGCT. DNA hypermethylation can cause gene silencing, including the inactivation of tumor suppressor genes. Many tumor suppressor genes have been found to be silenced in TGCT following DNA hypermethylation. Phthalates are endocrine disruptors and are abundantly used as industrial plasticizers. Di-2-(ethylhexyl) phthalate (DEHP) is the most common phthalate found in consumer products and has been reported to be associated with hypermethylation. After exposure, Di-2-(ethylhexyl) phthalate is rapidly hydrolyzed into its active form, mono-(2-ethylhexyl) phthalate (MEHP), a testicular toxicant. The purpose of this study is to examine gene promoter-region methylation in testicular cells and assess the relationship between exposure to phthalates and expression and methylation status of tumor suppressor genes: Testisin and RASSF1A. Alteration of gene expression of xenobiotic metabolizing enzymes is also known to be associated with TGCT, thus genes, such as GSTP1 and CYP1A2, will also be studied. Methods: Promoter hypermethylation and gene expression was examined for each genes in testicular germ cells exposed to MEHP in a dose- and time-dependent manner at concentrations of 10 nM, 1 μM, 10 μM, 100 μM, and 1 mM at 24-, 48,- 72-, and 96-hour points, respectively. The methylation status of the tumor suppressor genes Testisin, RASSF1A, and xenbiotic metabolizing enzyme genes: GSTP1 and CYP1A2 were assessed by methylation specific (MSP)-PCR and gene expression by qRT-PCR. Results: Exposures inversely increased cell proliferation, cell viability and methylation, and decreased gene expression. The results indicative of an association between DNA methylation and gene expression following exposure to phthalate will be presented and discussed. Conclusion: The findings of this study will allow for a better understanding of the role phthalates play in DNA methylation and the subsequent expression of methylated genes in testicular germ cells.
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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".