title: The presence of modified nucleosides in extracellular fluids leads to the specific incorporation of 5-chlorocytidine into RNA and modulates the transcription and translation.
abstract: Myeloperoxidase (MPO) is able to promote several kinds of damage and is involved in mechanisms leading to various diseases such as atherosclerosis or cancers. An example of these damages is the chlorination of nucleic acids, which is considered as a specific marker of the MPO activity. Since 5-chlorocytidine has been recently shown in healthy donor plasmas, this study aimed at discovering if these circulating modified nucleosides could be incorporated into RNA and DNA and if their presence impacts the ability of enzymes involved in the incorporation, transcription, and translation processes. Experimentations, which were carried out in vitro with endothelial and prostatic cells, showed a large penetration of all chloronucleosides but an exclusive incorporation of 5-chlorocytidine into RNA. However, no incorporation into DNA was observed. This specific incorporation is accompanied by an important reduction of translation yield. Although, in vitro, DNA polymerase processed in the presence of chloronucleosides but more slowly than in control conditions, ribonucleotide reductase could not reduce chloronucleotides prior to the replication. This reduction seems to be a limiting step, protecting DNA from chloronucleoside incorporation. This study shows the capacity of transcription enzyme to specifically incorporate 5-chlorocytidine into RNA and the loss of capacity-complete or partial-of different enzymes, involved in replication, transcription or translation, in the presence of chloronucleosides. Questions remain about the long-term impact of such specific incorporation in the RNA and such decrease of protein production on the cell viability and function.
authors.affiliation: Laboratory of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Noyon
authors.affiliation: Department of Urology, Erasme Hospital, Université Libre de Bruxelles, 1070, Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roumeguère
authors.affiliation: Laboratory of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium.|Analytical Platform of the Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Campus Plaine CP205/5, Boulevard du Triomphe, Brussels, 1050, Belgium.
authors.forename: Cédric
authors.initials: C
authors.lastname: Delporte
authors.affiliation: Laboratory of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Dufour
authors.affiliation: Laboratory of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium.|Analytical Platform of the Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Campus Plaine CP205/5, Boulevard du Triomphe, Brussels, 1050, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Cortese
authors.affiliation: Unit of Dialysis, CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, 6110, Montigny-le-Tilleul, Belgium.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Desmet
authors.affiliation: Laboratory of Experimental Medicine, CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, 6110, Montigny-le-Tilleul, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lelubre
authors.affiliation: Laboratory of Experimental Medicine, CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, 6110, Montigny-le-Tilleul, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Laboratory of Molecular Biology of Inflammation, IBMM, Faculty of Sciences, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Poelvoorde
authors.affiliation: Laboratory of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium.
authors.forename: Jean
authors.initials: J
authors.lastname: Nève
authors.affiliation: Laboratory of Molecular Biology of Inflammation, IBMM, Faculty of Sciences, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Vanhamme
authors.affiliation: Laboratory of Experimental Medicine, CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, 6110, Montigny-le-Tilleul, Belgium.
authors.forename: Karim Zouaoui
authors.initials: KZ
authors.lastname: Boudjeltia
authors.affiliation: Laboratory of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, 1050, Brussels, Belgium. pvantwer@ulb.ac.be.|Analytical Platform of the Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, Université Libre de Bruxelles, Campus Plaine CP205/5, Boulevard du Triomphe, Brussels, 1050, Belgium. pvantwer@ulb.ac.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Antwerpen
mesh_terms: D002478:Cells, Cultured; D002713:Chlorine / Q000737:chemistry; D003562:Cytidine / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology*; D045604:Extracellular Fluid / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D008297:Male; D009705:Nucleosides / Q000097:blood / Q000737:chemistry*; D009195:Peroxidase / Q000378:metabolism; D011467:Prostate / Q000166:cytology*; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis* / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D009705:Nucleosides; D002713:Chlorine; D003562:Cytidine; D012313:RNA; D009195:Peroxidase
keywords: 5-Chlorocytidine; Myeloperoxidase; Plasma; RNA; Transcription/translation