Retained sensitivity to cytotoxic pyrimidine nucleoside analogs in thymidine kinase 2 deficient human fibroblasts.
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.
Bjerke
Mia
M
Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
Solaroli
Nicola
N
Lesko
Nicole
N
Balzarini
Jan
J
Johansson
Magnus
M
Karlsson
Anna
A
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
D004272:DNA, Mitochondrial; D011741:Pyrimidine Nucleosides; C020235:brivudine; C105339:thymidine kinase 2; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine