A new technique for the analysis of metabolic pathways of cytidine analogues and cytidine deaminase activities in cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 Nov 2023
22 Nov 2023
Historique:
received:
15
10
2023
accepted:
18
11
2023
medline:
24
11
2023
pubmed:
23
11
2023
entrez:
22
11
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37993628
doi: 10.1038/s41598-023-47792-4
pii: 10.1038/s41598-023-47792-4
pmc: PMC10665361
doi:
Substances chimiques
Cytidine
5CSZ8459RP
DCMP Deaminase
EC 3.5.4.12
Deoxycytidine Kinase
EC 2.7.1.74
Deoxycytidine
0W860991D6
Cytidine Deaminase
EC 3.5.4.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20530Subventions
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU22-08-00148
Informations de copyright
© 2023. The Author(s).
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