Altered deoxyribonucleotide pools in T-lymphoblastoid cells expressing the multisubstrate nucleoside kinase of Drosophila melanogaster

摘要: The multisubstrate nucleoside kinase of Drosophila melanogaster (Dm-dNK) can be expressed in human solid tumor cells and its unique enzymatic properties makes this enzyme a suicide gene candidate. In the present study, Dm-dNK was stably CCRF-CEM H9 T-lymphoblastoid cell lines. localized to nucleus retained activity. overexpressing showed ≈ 200-fold increased sensitivity cytostatic activity several analogs, such as pyrimidine analogs (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) 1-β-d-arabinofuranosylthymine (araT), but not antiherpetic purine ganciclovir, acyclovir penciclovir, which may allow technology applied donor T and/or rescue graft vs. host disease permit modulation alloreactivity after transplantation. most pronounced effect on steady-state dNTP levels two- 10-fold dTTP pool expressing that were grown presence 1 µm each natural deoxyribonucleoside. Although demonstrated imbalances, no mitochondrial DNA deletions or altered detected H9 Dm-dNK cells.