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In vivo evidence of ascorbate involvement in the generation of epigenetic DNA modifications in leukocytes from patients with colorectal carcinoma, benign adenoma and inflammatory bowel disease.
Starczak, Marta; Zarakowska, Ewelina; Modrzejewska, Martyna; Dziaman, Tomasz; Szpila, Anna; Linowiecka, Kinga; Guz, Jolanta; Szpotan, Justyna; Gawronski, Maciej; Labejszo, Anna; Liebert, Ariel; Banaszkiewicz, Zbigniew; Klopocka, Maria; Foksinski, Marek; Gackowski, Daniel; Olinski, Ryszard.
Afiliação
  • Starczak M; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Zarakowska E; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Modrzejewska M; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Dziaman T; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Szpila A; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Linowiecka K; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Guz J; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Szpotan J; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Gawronski M; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Labejszo A; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Liebert A; Department of Vascular Diseases and Internal Medicine, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Ujejskiego 75, 85-168, Bydgoszcz, Poland.
  • Banaszkiewicz Z; Department of Vascular Surgery and Angiology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, M. Curie Sklodowskiej 9, 85-094, Bydgoszcz, Poland.
  • Klopocka M; Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University No. 2 in Bydgoszcz, Ujejskiego 75, 85-168, Bydgoszcz, Poland.
  • Foksinski M; Department of Vascular Diseases and Internal Medicine, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Ujejskiego 75, 85-168, Bydgoszcz, Poland.
  • Gackowski D; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland.
  • Olinski R; Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karlowicza 24, 85-092, Bydgoszcz, Poland. danielg@cm.umk.pl.
J Transl Med ; 16(1): 204, 2018 07 20.
Article em En | MEDLINE | ID: mdl-30029654
BACKGROUND: A characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA. METHODS: The study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136). The list of analyzed parameters included (i) leukocyte levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine, a marker of oxidatively modified DNA, determined by means of isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, (ii) expression of TET mRNA measured with RT-qPCR, and (iii) chromatographically-determined plasma concentrations of retinol, alpha-tocopherol and ascorbate. RESULTS: Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine in DNA than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of ascorbate and retinol. A positive correlation was observed between plasma concentration of ascorbate and levels of two epigenetic modifications, 5-hydroxymethylcytosine and 5-hydroxymethyluracil in leukocyte DNA. Moreover, a significant difference was found in the levels of these modifications in patients whose plasma concentrations of ascorbate were below the lower and above the upper quartile for the control group. CONCLUSIONS: These findings suggest that deficiency of ascorbate in the blood may be a marker of its shortage in other tissues, which in turn may correspond to deterioration of DNA methylation-demethylation. These observations may provide a rationale for further research on blood biomarkers of colorectal cancer development.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Ascórbico / DNA / Neoplasias Colorretais / Doenças Inflamatórias Intestinais / Adenoma / Epigênese Genética / Leucócitos Tipo de estudo: Observational_studies Limite: Aged / Female / Humans / Male Idioma: En Revista: J Transl Med Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Ascórbico / DNA / Neoplasias Colorretais / Doenças Inflamatórias Intestinais / Adenoma / Epigênese Genética / Leucócitos Tipo de estudo: Observational_studies Limite: Aged / Female / Humans / Male Idioma: En Revista: J Transl Med Ano de publicação: 2018 Tipo de documento: Article