Dr Jekyll and Mr Hyde: a strange case of 5-ethynyl-2 '-deoxyuridine and 5-ethynyl-2 '- deoxycytidine

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00458684" target="_blank" >RIV/61388963:_____/16:00458684 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/16:33155325

Výsledek na webu

<a href="http://rsob.royalsocietypublishing.org/content/6/1/150172" target="_blank" >http://rsob.royalsocietypublishing.org/content/6/1/150172</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1098/rsob.150172" target="_blank" >10.1098/rsob.150172</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dr Jekyll and Mr Hyde: a strange case of 5-ethynyl-2 '-deoxyuridine and 5-ethynyl-2 '- deoxycytidine

Popis výsledku v původním jazyce

5-Ethynyl-2 '-deoxyuridine (EdU) and 5-ethynyl-2 '-deoxycytidine (EdC) are mainly used as markers of cellular replicational activity. Although EdU is employed as a replicational marker more frequently than EdC, its cytotoxicity is commonly much higher than the toxicity of EdC. To reveal the reason of the lower cytotoxicity of EdC, we performed a DNA analysis of five EdC-treated human cell lines. Surprisingly, not a single one of the tested cell lines contained a detectable amount of EdC in their DNA. Instead, the DNA of all the cell lines contained EdU. The content of incorporated EdU differed in particular cells and EdC-related cytotoxicity was directly proportional to the content of EdU. The results of experiments with the targeted inhibition of the cytidine deaminase (CDD) and dCMP deaminase activities indicated that the dominant role in the conversion pathway of EdC to EdUTP is played by CDD in HeLa cells. Our results also showed that the deamination itself was not able to effectively prevent the conversion of EdC to EdCTP, the conversion of EdC to EdCTP occurs with much lesser effectivity than the conversion of EdU to EdUTP and the EdCTP is not effectively recognized by the replication complex as a substrate for the synthesis of nuclear DNA.

Název v anglickém jazyce

Dr Jekyll and Mr Hyde: a strange case of 5-ethynyl-2 '-deoxyuridine and 5-ethynyl-2 '- deoxycytidine

Popis výsledku anglicky

5-Ethynyl-2 '-deoxyuridine (EdU) and 5-ethynyl-2 '-deoxycytidine (EdC) are mainly used as markers of cellular replicational activity. Although EdU is employed as a replicational marker more frequently than EdC, its cytotoxicity is commonly much higher than the toxicity of EdC. To reveal the reason of the lower cytotoxicity of EdC, we performed a DNA analysis of five EdC-treated human cell lines. Surprisingly, not a single one of the tested cell lines contained a detectable amount of EdC in their DNA. Instead, the DNA of all the cell lines contained EdU. The content of incorporated EdU differed in particular cells and EdC-related cytotoxicity was directly proportional to the content of EdU. The results of experiments with the targeted inhibition of the cytidine deaminase (CDD) and dCMP deaminase activities indicated that the dominant role in the conversion pathway of EdC to EdUTP is played by CDD in HeLa cells. Our results also showed that the deamination itself was not able to effectively prevent the conversion of EdC to EdCTP, the conversion of EdC to EdCTP occurs with much lesser effectivity than the conversion of EdU to EdUTP and the EdCTP is not effectively recognized by the replication complex as a substrate for the synthesis of nuclear DNA.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/NV15-31604A" target="_blank" >NV15-31604A: Cílené poškození DNA opravných mechanismů jako prostředek léčby rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Open Biology

ISSN

2046-2441

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

—

Kód UT WoS článku

000368938200003

EID výsledku v databázi Scopus

2-s2.0-84962256431