Dergiler / Turkish Journal of Pharmaceutical Sciences / 2020 / Cilt: 17 - Sayı: 3

Global DNA Hypomethylation and Rassf1a and c-myc Promoter Hypermethylation in Rat Kidney Cells after Bisphenol A Exposure

Bisfenol A Maruziyeti Sonrası Sıçan Böbrek Hücrelerinde Global DNA Hipometilasyonu ve Rassf1a ile c-myc Promotör Hipermetilasyonu

Sayfa
337–342
DOI
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Expression levels of Rassf1a and c-myc changed in response to BPA at the high concentrations after 24 h treatment, whereas 100nM exposure to BPA altered gene expression after 48, 72, and 96 h.Conclusion: These results indicate that changes in global and gene-specific DNA methylation may play an important role in the mechanism of BPAtoxicity in kidney cells.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Objectives: Bisphenol A (BPA) is a synthetic monomer used in the production of polycarbonate and an environmental contaminant with endocrinedisrupting properties.
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Temel Bulgular & Veri:BPA release from plastic carriers is thought to cause high amounts of exposure, which result in high risk to human andenvironment health.Materials and Methods: The study examined the possible changes in global DNA methylation, CpG promoter DNA methylation, and gene expressionsof Rassf1a and c-myc after BPA exposure in rat kidney epithelial cells (NRK-52E).Results: The IC50 values of BPA in NRK-52E cells were 133.42 and 101.74 µM in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and neutral red uptake tests, respectively.
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Sonuç & Katkı:Expression levels of Rassf1a and c-myc changed in response to BPA at the high concentrations after 24 h treatment, whereas 100nM exposure to BPA altered gene expression after 48, 72, and 96 h.Conclusion: These results indicate that changes in global and gene-specific DNA methylation may play an important role in the mechanism of BPAtoxicity in kidney cells.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Alan Parametreleri

Özet

Objectives: Bisphenol A (BPA) is a synthetic monomer used in the production of polycarbonate and an environmental contaminant with endocrinedisrupting properties. BPA release from plastic carriers is thought to cause high amounts of exposure, which result in high risk to human andenvironment health.Materials and Methods: The study examined the possible changes in global DNA methylation, CpG promoter DNA methylation, and gene expressionsof Rassf1a and c-myc after BPA exposure in rat kidney epithelial cells (NRK-52E).Results: The IC50 values of BPA in NRK-52E cells were 133.42 and 101.74 µM in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and neutral red uptake tests, respectively. The cells were treated with BPA at 1 nM, 10 nM, 100 nM, 1 µM, and 10 µM concentrations for 24 hand at 100 nM concentration for 24, 48, 72, 96 h, and 6 days. Decreased global 5-methylcytosine levels were observed after 48, 72, 96 h, and 6 daysat the concentration of 100 nM BPA. Changes in CpG promoter DNA methylation were detected in the genes of Rassf1a and c-myc in BPA-treatedNRK-52E cells. Expression levels of Rassf1a and c-myc changed in response to BPA at the high concentrations after 24 h treatment, whereas 100nM exposure to BPA altered gene expression after 48, 72, and 96 h.Conclusion: These results indicate that changes in global and gene-specific DNA methylation may play an important role in the mechanism of BPAtoxicity in kidney cells.

Abstract

Amaç: Bisfenol A (BPA), polikarbonat üretiminde kullanılan sentetik bir monomerdir ve çevresel bir kontaminant olup endokrin bozucu özelliklere sahiptir. BPA’nın plastik taşıyıcılardan salınması yüksek oranda maruziyete sebep olabilir, bu durum insan ve çevre sağlığı üzerinde yüksek oranda riske sebep olabilir. Gereç ve Yöntemler: Bu çalışmada, BPA’nın sıçan böbrek epitel hücrelerinde (NRK-52E) global DNA metilasyonu, Rassf1a ve c-myc genlerinin CpG promotör bölge DNA metilasyonu ve gen ekspresyonu üzerinde oluşturabileceği değişikliklerin araştırıldı. Bulgular: BPA’nın IC50 değeri NRK-52E hücrelerinde 3-(4,5-dimethylthiazol-2-yl)-2,5-difenil tetrazolium bromid ve nötral kırmızı alım testi ile sırasıyla 105 µM ve 88 µM olarak bulundu. Hücreler 1 nM, 10 nM, 100 nM, 1 µM ve 10 µM konsantrasyonlarda BPA’ya 24 saat boyunca ve 100 nM konsantrasyonda BPA’ya 24, 48, 72, 96 saat ve 6 gün boyunca maruz bırakıldı. 48, 72, 96 saat ve 6 gün sonra 100 nM BPA konsantrasyonunda global 5-metilsitozin seviyelerinde azalma gözlendi. BPA’ya maruz bırakılmış NRK-52E hücrelerinde Rassf1a ve c-myc genlerinin CpG promotör bölgelerinde metilasyonda değişiklikler tespit edildi. Rassf1a ve c-myc genlerinin ekspresyon seviyeleri yüksek konsantrasyonlarda 24 saat BPA maruziyet ile ve 100 nM konsantrasyonda 48, 72 ve 96 saat BPA maruziyetleri ile değişiklik gösterdi. Sonuç: Bu sonuçlar, böbrek hücrelerinde global ve gene özgü DNA metilasyonundaki değişikliklerin BPA’nın toksisite mekanizmasında önemli bir rol oynayabileceğini göstermektedir.

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Bu Makaleye Atıf Yap

TUZCUOĞLU, P., ÖZDEN, S. (2020). Global DNA Hypomethylation and Rassf1a and c-myc Promoter Hypermethylation in Rat Kidney Cells after Bisphenol A Exposure. Turkish Journal of Pharmaceutical Sciences, Cilt: 17 - Sayı: 3, 337–342. https://ajindex.com/articles/403931

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