Differential incorporation of 1-beta-D-arabinofuranosylcytosine and 9-beta-D-arabinofuranosylguanine into nuclear and mitochondrial DNA.
The anti-leukemic nucleoside analogs 1-beta-D-arabinofuranosylcytosine (araC) and 9-beta-D-arabinofuranosylguanine (araG) are dependent on intracellular phosphorylation for pharmacological activity. AraC is efficiently phosphorylated by deoxycytidine kinase (dCK). Although araG is phosphorylated by dCK in vitro, it is a preferred substrate of mitochondrial deoxyguanosine kinase. We have used autoradiography to show that araC was incorporated into nuclear DNA in Molt-4 and CEM T-lymphoblastoid cells as well as in Chinese hamster ovary cells. In contrast, araG was predominantly incorporated into mitochondrial DNA in the investigated cell lines, without detectable incorporation into nuclear DNA. These data suggest that the molecular targets of araG and araC may differ.
Zhu
C
C
Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, S-141 86, Stockholm, Sweden.
Johansson
M
M
Karlsson
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D001087:Arabinonucleosides / Q000378:metabolism*; D001345:Autoradiography; D016466:CHO Cells; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003561:Cytarabine / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003842:Deoxycytidine Kinase / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D014162:Transfection
D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D004272:DNA, Mitochondrial; D003561:Cytarabine; C028771:9-arabinofuranosylguanine; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); C105339:thymidine kinase 2; C019165:deoxyguanosine kinase; D013937:Thymidine Kinase; D003842:Deoxycytidine Kinase