P19 Neuronal Differentiation and Retinoic Acid Metabolism as Criteria to Investigate Atrazine, Nitrite, and Nitrate Developmental Toxicity
| العنوان: | P19 Neuronal Differentiation and Retinoic Acid Metabolism as Criteria to Investigate Atrazine, Nitrite, and Nitrate Developmental Toxicity |
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| المؤلفون: | Philippe Ducharme, Mathieu Solari, Monique Boily, Joanne Paquin |
| المصدر: | Toxicological Sciences. 113:116-126 |
| بيانات النشر: | Oxford University Press (OUP), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Time Factors, Cell Survival, medicine.drug_class, Cellular differentiation, Developmental toxicity, Retinoic acid, Lewis X Antigen, Tretinoin, Biology, Toxicology, Risk Assessment, Cell Line, Mice, chemistry.chemical_compound, Tubulin, medicine, Animals, Retinoid, Nitrite, Fertilizers, Chromatography, High Pressure Liquid, Embryonic Stem Cells, Cell Proliferation, Neurons, Nitrates, Dose-Response Relationship, Drug, Sodium Nitrite, Cell Differentiation, Flow Cytometry, Teratogens, P19 cell, Biochemistry, chemistry, Neuron differentiation, Atrazine, Biomarkers, Water Pollutants, Chemical, Environmental Monitoring, medicine.drug |
| الوصف: | Atrazine and nitrogenous fertilizers are agrochemical contaminants frequently detected in water systems in North America. Several studies reported their ability to affect amphibian and mammalian development. Retinoids, supplied in the diet or synthesized by cells, are essential to embryogenesis. Disturbance of their homeostasis may lead to teratogenic effects. Retinoic acid (RA) is a major retinoid regulator of cell proliferation and differentiation. Previous studies reported alterations of retinoid stores in bullfrogs of Yamaska River subwatersheds (Québec, Canada), a region of intensive agricultural activities associated with atrazine, nitrate, and nitrite contaminants. These contaminants could affect RA metabolism and RA-mediated processes. Mouse P19 embryonic stem cells, which can differentiate to neurons in response to RA, were used to test this hypothesis. Cells were cultured in the absence or presence of contaminants during neuroinduction with RA and assayed by flow cytometry for expression of stage-specific embryonic antigen-1 (SSEA1) (embryonic marker) and betaIII-tubulin (neuronal marker). Cell cultures were also analyzed for RA metabolism by high performance liquid chromotagraphy (HPLC). Downregulation of SSEA1 paralleled betaIII-tubulin upregulation in an RA concentration-dependent manner. Atrazine, nitrate, and nitrite did not affect differentiation at environmentally encountered micromolar concentrations. However, low molar nitrite prevented RA-induced SSEA1 downregulation and decreased betaIII-tubulin appearance. Decreased cell viability/proliferation accompanied these differentiation effects. P19 cells metabolized RA to polar retinoids. RA metabolism was not affected at any concentration of atrazine, nitrate, or nitrite. Environmentally relevant levels of these contaminants, thus, had no gross effect on neurodifferentiation and RA catabolism of embryonic stem cells. P19 cell-based bioassays may provide valuable tools in monitoring developmental toxicity. |
| تدمد: | 1096-0929 1096-6080 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41f703dc11a2841b1ce8a8d2afddc09aTest https://doi.org/10.1093/toxsci/kfp243Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....41f703dc11a2841b1ce8a8d2afddc09a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10960929 10966080 |
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