A new technique for the analysis of metabolic pathways of cytidine analogues and cytidine deaminase activities in cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F23%3A73620535" target="_blank" >RIV/61989592:15110/23:73620535 - isvavai.cz</a>

Alternative codes found

RIV/00098892:_____/23:10158302

Result on the web

<a href="https://www.nature.com/articles/s41598-023-47792-4" target="_blank" >https://www.nature.com/articles/s41598-023-47792-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-023-47792-4" target="_blank" >10.1038/s41598-023-47792-4</a>

Result language

angličtina

Original language name

A new technique for the analysis of metabolic pathways of cytidine analogues and cytidine deaminase activities in cells

Original language description

Deoxycytidine analogues (dCas) are widely used for the treatment of malignant diseases. They are commonly inactivated by cytidine deaminase (CDD), or by deoxycytidine monophosphate deaminase (dCMP deaminase). Additional metabolic pathways, such as phosphorylation, can substantially contribute to their (in)activation. Here, a new technique for the analysis of these pathways in cells is described. It is based on the use of 5-ethynyl 2′-deoxycytidine (EdC) and its conversion to 5-ethynyl 2′-deoxyuridine (EdU). Its use was tested for the estimation of the role of CDD and dCMP deaminase in five cancer and four non-cancer cell lines. The technique provides the possibility to address the aggregated impact of cytidine transporters, CDD, dCMP deaminase, and deoxycytidine kinase on EdC metabolism. Using this technique, we developed a quick and cheap method for the identification of cell lines exhibiting a lack of CDD activity. The data showed that in contrast to the cancer cells, all the non-cancer cells used in the study exhibited low, if any, CDD content and their cytidine deaminase activity can be exclusively attributed to dCMP deaminase. The technique also confirmed the importance of deoxycytidine kinase for dCas metabolism and indicated that dCMP deaminase can be fundamental in dCas deamination as well as CDD. Moreover, the described technique provides the possibility to perform the simultaneous testing of cytotoxicity and DNA replication activity.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NU22-08-00148" target="_blank" >NU22-08-00148: The impact of cytidine metabolic pathways on cytarabine therapy of hematological malignancies and new diagnostic tools for their analysis</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

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

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

20530

UT code for WoS article

001124641700080

EID of the result in the Scopus database

2-s2.0-85177662424