[PMID]: | 29190698 |
[Au] Autor: | Foksinski M; Zarakowska E; Gackowski D; Skonieczna M; Gajda K; Hudy D; Szpila A; Bialkowski K; Starczak M; Labejszo A; Czyz J; Rzeszowska-Wolny J; Olinski R |
[Ad] Endereço: | Department of Clinical Biochemistry, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland. |
[Ti] Título: | Profiles of a broad spectrum of epigenetic DNA modifications in normal and malignant human cell lines: Proliferation rate is not the major factor responsible for the 5-hydroxymethyl-2'-deoxycytidine level in cultured cancerous cell lines. |
[So] Source: | PLoS One;12(11):e0188856, 2017. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Active demethylation of 5-methylcytosine moiety in DNA occurs by its sequential oxidation to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, catalysed by enzymes of the Ten-Eleven Translocation family proteins (TETs 1, 2 and 3). Here we analyzed for the first time all the intermediate products of DNA demethylation pathway in the form of deoxynucleosides (5-methyl-2'-deoxycytidine, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine as well as 5-(hydroxymethyl)-2'-deoxyuridine) using automated isotope-dilution online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry. DNA was isolated from human malignant cell lines of colon adenocarcinoma (HCT 116), melanoma (Me45), myelogenous leukemia bone marrow blasts (K562), EBV-positive Burkitt's lymphoma lymphoblasts (Raji), EBV-negative Burkitt's lymphoma lymphoblasts (male-CA46 and female-ST486), as well as normal neonatal dermal fibroblasts (NHDF-Neo). The expression levels of TET1, TET2, TET3, SMUG1, and TDG genes were also assayed by RT-qPCR. Our results show a global erasure of 5-hydroxymethyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine in DNA of cultured cells compared with DNA from primary malignant tissue. Moreover, malignant cells in culture have a quite different DNA epigenetic profile than cultured normal cells, and different types of malignant cells display different and characteristic profiles of DNA epigenetic marks. Similar analyses of a broader spectrum of epigenetic modifications, not restricted to 5-methyl-2'-deoxycytidine, could lead to better understanding of the mechanism(s) responsible for emergence of different types of cancer cells. |
[Mh] Termos MeSH primário: |
Proliferação Celular/efeitos dos fármacos DNA/genética Desoxicitidina/análogos & derivados Epigênese Genética
|
[Mh] Termos MeSH secundário: |
Linhagem Celular Tumoral Cromatografia Líquida Citosina/análise DNA/química Desoxicitidina/farmacologia Seres Humanos Reação em Cadeia da Polimerase em Tempo Real Reação em Cadeia da Polimerase Via Transcriptase Reversa Espectrometria de Massas em Tandem Timina/análise
|
[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (5-hydroxymethyl-2'-deoxycytidine); 0W860991D6 (Deoxycytidine); 8J337D1HZY (Cytosine); 9007-49-2 (DNA); QR26YLT7LT (Thymine) |
[Em] Mês de entrada: | 1712 |
[Cu] Atualização por classe: | 171226 |
[Lr] Data última revisão:
| 171226 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171201 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0188856 |
|
|