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
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1581-9 |
| _version_ | 1819054470029377536 |
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| author | Marta Starczak Ewelina Zarakowska Martyna Modrzejewska Tomasz Dziaman Anna Szpila Kinga Linowiecka Jolanta Guz Justyna Szpotan Maciej Gawronski Anna Labejszo Ariel Liebert Zbigniew Banaszkiewicz Maria Klopocka Marek Foksinski Daniel Gackowski Ryszard Olinski |
| author_facet | Marta Starczak Ewelina Zarakowska Martyna Modrzejewska Tomasz Dziaman Anna Szpila Kinga Linowiecka Jolanta Guz Justyna Szpotan Maciej Gawronski Anna Labejszo Ariel Liebert Zbigniew Banaszkiewicz Maria Klopocka Marek Foksinski Daniel Gackowski Ryszard Olinski |
| author_sort | Marta Starczak |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T12:52:08Z |
| format | Article |
| id | doaj.art-507636277e8b48f1a1b4f317954fc4dc |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T12:52:08Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-507636277e8b48f1a1b4f317954fc4dc2022-12-21T19:03:27ZengBMCJournal of Translational Medicine1479-58762018-07-0116111110.1186/s12967-018-1581-9In vivo evidence of ascorbate involvement in the generation of epigenetic DNA modifications in leukocytes from patients with colorectal carcinoma, benign adenoma and inflammatory bowel diseaseMarta Starczak0Ewelina Zarakowska1Martyna Modrzejewska2Tomasz Dziaman3Anna Szpila4Kinga Linowiecka5Jolanta Guz6Justyna Szpotan7Maciej Gawronski8Anna Labejszo9Ariel Liebert10Zbigniew Banaszkiewicz11Maria Klopocka12Marek Foksinski13Daniel Gackowski14Ryszard Olinski15Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Vascular Diseases and Internal Medicine, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Vascular Surgery and Angiology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Vascular Diseases and Internal Medicine, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńAbstract 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.http://link.springer.com/article/10.1186/s12967-018-1581-9Epigenetic DNA modificationsDNA demethylationColorectal cancerIBDColon polypAscorbate |
| spellingShingle | Marta Starczak Ewelina Zarakowska Martyna Modrzejewska Tomasz Dziaman Anna Szpila Kinga Linowiecka Jolanta Guz Justyna Szpotan Maciej Gawronski Anna Labejszo Ariel Liebert Zbigniew Banaszkiewicz Maria Klopocka Marek Foksinski Daniel Gackowski Ryszard Olinski 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 Journal of Translational Medicine Epigenetic DNA modifications DNA demethylation Colorectal cancer IBD Colon polyp Ascorbate |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Epigenetic DNA modifications DNA demethylation Colorectal cancer IBD Colon polyp Ascorbate |
| url | http://link.springer.com/article/10.1186/s12967-018-1581-9 |
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