title: Retained sensitivity to cytotoxic pyrimidine nucleoside analogs in thymidine kinase 2 deficient human fibroblasts.
abstract: Thymidine kinase 2 (TK2) is a mitochondrial deoxyribonucleoside kinase that phosphorylates several nucleoside analogs used in anti-viral and anti-cancer therapy. A fibroblast cell line with decreased TK2 activity was investigated in order to obtain insights in the effects of TK2 deficiency on nucleotide metabolism. The role of TK2 for the sensitivity against cytotoxic nucleoside analogs was also investigated. The TK2 deficient cells retained their sensitivity against all pyrimidine nucleoside analogs tested. This study suggests that nucleoside analog phosphorylation mediated by TK2 may be less important, compared to other deoxyribonucleoside kinases, for the cytotoxic effects of these compounds.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Bjerke
authors.forename: Nicola
authors.initials: N
authors.lastname: Solaroli
authors.forename: Nicole
authors.initials: N
authors.lastname: Lesko
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Magnus
authors.initials: M
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D011741:Pyrimidine Nucleosides; C020235:brivudine; C105339:thymidine kinase 2; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine