Effects of Neonicotinoids on Promoter-Specific Expression and Activity of Aromatase (CYP19) in Human Adrenocortical Carcinoma (H295R) and Primary Umbilical Vein Endothelial (HUVEC) Cells
Bibliographic record
Abstract
The enzyme aromatase (CYP19; cytochrome P450 19) in humans undergoes highly tissue- and promoter-specific regulation. In hormone-dependent breast cancer, aromatase is over-expressed via several normally inactive promoters (PII, I.3, I.7). Aromatase biosynthesizes estrogens, which stimulate breast cancer cell proliferation. The placenta produces estrogens required for healthy pregnancy and the major placental CYP19 promoter is I.1. Exposure to certain pesticides, such as atrazine, is associated with increased CYP19 expression, but little is known about the effects of neonicotinoid insecticides on CYP19. We developed sensitive and robust RT-qPCR methods to detect the promoter-specific expression of CYP19 in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells, and determined the potential promoter-specific disruption of CYP19 expression by atrazine and the commonly used neonicotinoids imidacloprid, thiacloprid, and thiamethoxam. In H295R cells, atrazine concentration-dependently increased PII- and I.3-mediated CYP19 expression and aromatase catalytic activity. Thiacloprid and thiamethoxam induced PII- and I.3-mediated CYP19 expression and aromatase activity at relatively low concentrations (0.1-1.0 µM), exhibiting non-monotonic concentration-response curves with a decline in gene induction and catalytic activity at higher concentrations. In HUVEC cells, atrazine slightly induced overall (promoter-indistinct) CYP19 expression (30 µM) and aromatase activity (≥ 3 µM), without increasing I.1 promoter activity. None of the neonicotinoids increased CYP19 expression or aromatase activity in HUVEC cells. Considering the importance of promoter-specific (over)expression of CYP19 in disease (breast cancer) or during sensitive developmental periods (pregnancy), our newly developed RT-qPCR methods will be helpful tools in assessing the risk that neonicotinoids and other chemicals may pose to exposed women.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".