Vitamin C enhances substantially formation of 5-hydroxymethyluracil in cellular DNA

Modrzejewska, Martyna; Gawroński, Maciej; Skonieczna, Magdalena; Zarakowska, Ewelina; Starczak, Marta; Foksiński, Marek; Rzeszowska-Wolny, Joanna; Gackowski, Daniel; Oliński, Ryszard

doi:10.1016/j.freeradbiomed.2016.10.535

Cited by 29 publications

(34 citation statements)

References 35 publications

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“…Recently, we have reported a spectacular increase in 5-hmUra content resulting from stimulation with vitamin C [16]. In turn, our present study demonstrated a positive correlation between plasma concentration of vitamin C and the levels of two epigenetic modifications, 5-hmCyt and 5-hmUra, in leukocyte DNA ( Figure S1).…”

Section: Discussionsupporting

confidence: 79%

“…30%) reduced levels of vitamin C [13,14]. Recent studies showed that ascorbate may enhance generation of 5-hmCyt in cultured cells [15][16][17][18]. Also vitamin A has been recently demonstrated to enhance 5-hmCyt synthesis and to modulate TET level [19].…”

Section: Introductionmentioning

confidence: 99%

“…A few previous studies demonstrated that ascorbate may enhance generation of 5-hmCyt in cultured cells, probably acting as a cofactor of TETs during hydroxylation of 5-mCyt [15][16][17][18].…”

mentioning

confidence: 99%

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Distinct pattern of epigenetic DNA modification in leukocytes from patients with colorectal carcinoma and individuals with precancerous conditions, benign adenoma and inflammatory bowel disease – a link to oxidative stress

Starczak

Zarakowska

Modrzejewska

et al. 2017

Preprint

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A characteristic feature of malignant cells, including colorectal cancer cells, is a profound decrease in level of 5-hydroxymethylcytosine, product of 5-methylcytosine oxidation by TET enzymes. This study included four groups of subjects: healthy controls, and patients with inflammatory bowel disease (IBD), benign polyps and colorectal cancer. Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine 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 vitamin C and A. Expressions of TET1 and TET2 turned out to be the highest in IBD group. To the best of our knowledge, this is the first study to show that healthy subjects, individuals with precancerous conditions and colorectal cancer patients present with distinct specific patterns of epigenetic modifications in leukocyte DNA.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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Distinct pattern of epigenetic DNA modification in leukocytes from patients with colorectal carcinoma and individuals with precancerous conditions, benign adenoma and inflammatory bowel disease – a link to oxidative stress

Starczak

Zarakowska

Modrzejewska

et al. 2017

Preprint

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“…[131] Another interesting observation is that high doses of vitamin Cc an lead to increased levels of hmdU and fdC, whereas hmdC reaches saturation already at lower vitamin C levels. [132] Taking these data together,w es uggest that the TET-induced formation of hmdU serves apurpose and that it is not merely al esion. This idea would be in line with the recent suggestions that 8-oxo-dG,a sa no xidation product of dG,might have gene regulatory roles as well.…”

Section: Discovery Of Oxidized Bases Beyond Hmdcmentioning

confidence: 98%

Non‐canonical Bases in the Genome: The Regulatory Information Layer in DNA

et al. 2018

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Multicellular organisms developed the concept of specialized cells that perform specific functions. Examples are neurons and fibroblast to name just two out of more than 200. These cellular differences are established based on the same sequence information stored in the cell nucleus of all cells of an organism. The sequence information needs consequently different interpretations by the different cell types. During cellular development this interpretation of the genetic code has to be tightly regulated in space and time. Interpretation of the sequence information involves the controlled activation and silencing of specific genes so that certain proteins are made in one cell type but not in others. This involves an additional regulatory information layer beyond the pure base sequence. One aspect of this regulatory information layer relies on functional groups that are attached to the C(5) position of the canonical base dC. Currently four regulatory, non-canonical bases with a methyl (CH )-, a hydroxymethyl (CH OH)-, a formyl (CHO)- and a carboxyl (COOH)- group are known. While 5-methyl-cytidine is long recognised to be a regulatory base in the genome, the other three bases and the enzymes responsible for generating them, were just recently discovered.

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“…Diese Beobachtung konnte kürzlich in einer Studie, bei der ein TET‐Enzym aus Naegleria verwendet wurde, bestätigt werden . Interessant ist außerdem, dass hohe Vitamin‐C‐Dosen steigende Mengen an hmdU und fdC erzeugen, der hmdC‐Wert jedoch schon bei einer relativ geringen Vitamin‐C‐Konzentration eine Sättigung zeigt . Durch Betrachtung all dieser Daten in einem größeren Kontext kamen wir zu der Erkenntnis, dass hmdU vermutlich eine spezifische Funktion ausübt und nicht nur ein Oxidationsschaden ist.…”

Section: Entdeckung Oxidierter Basen Jenseits Von Hmdcunclassified

Nichtkanonische Basen im Genom: die regulative Informationsebene in der DNA

et al. 2018

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In multizellulären Organismen findet man spezialisierte Zellen, die jeweils eine bestimmte Funktion wahrnehmen. Diese zellulären Unterschiede beruhen alle auf der identischen Sequenzinformation, die im Zellkern gespeichert ist. Daher muss diese Sequenzinformation von den verschiedenen Zelltypen unterschiedlich interpretiert werden. Während des frühen Entwicklungsstadiums einer Zelle muss diese Übersetzung räumlich und zeitlich streng kontrolliert werden. Die jeweilige Interpretation der Sequenzinformation umfasst die kontrollierte Aktivierung und Stilllegung spezifischer Gene, sodass ein Protein nur in bestimmten Zellen exprimiert wird. Dafür ist eine weitere Informationsebene vonnöten, die sich von der reinen Basensequenz abhebt. Ein Aspekt dieser regulatorischen Informationsebene beruht auf funktionellen Gruppen an der C5‐Position der kanonischen Base dC. Heute kennt man vier dieser regulatorischen, nichtkanonischen Basen, die eine CH3‐, CH2OH‐, CHO‐ oder COOH‐Gruppe aufweisen. Während 5‐Methylcytidin schon lange als eine der Basen im Genom mit dieser Funktion bekannt ist, wurden die anderen drei Basen – und die für die Entstehung verantwortlichen Enzyme – erst kürzlich entdeckt.

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Vitamin C enhances substantially formation of 5-hydroxymethyluracil in cellular DNA

Cited by 29 publications

References 35 publications

Distinct pattern of epigenetic DNA modification in leukocytes from patients with colorectal carcinoma and individuals with precancerous conditions, benign adenoma and inflammatory bowel disease – a link to oxidative stress

Distinct pattern of epigenetic DNA modification in leukocytes from patients with colorectal carcinoma and individuals with precancerous conditions, benign adenoma and inflammatory bowel disease – a link to oxidative stress

Non‐canonical Bases in the Genome: The Regulatory Information Layer in DNA

Nichtkanonische Basen im Genom: die regulative Informationsebene in der DNA

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