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Differential incorporation of 1‐β‐ D ‐arabinofuranosylcytosine and 9‐β‐ D ‐arabinofuranosylguanine into nuclear and mitochondrial DNA
Author(s) -
Zhu Chaoyong,
Johansson Magnus,
Karlsson Anna
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01569-6
Subject(s) - deoxycytidine kinase , chinese hamster ovary cell , deoxyguanosine , microbiology and biotechnology , chemistry , nuclear dna , phosphorylation , biochemistry , mitochondrion , dna , mitochondrial dna , biology , deoxycytidine , genetics , receptor , chemotherapy , gemcitabine , gene
The anti‐leukemic nucleoside analogs 1‐β‐ D ‐arabinofuranosylcytosine (araC) and 9‐β‐ 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.