Bacterial deoxyribonucleoside kinases are poor suicide genes in mammalian cells.

Abstract

Transfer of deoxyribonucleoside kinases (dNKs) into cancer cells increases the activity of cytotoxic nucleoside analogues. It has been shown that bacterial dNKs, when introduced into Escherichia coli, sensitize this bacterium toward nucleoside analogues. We studied the possibility of using bacterial dNKs, for example deoxyadenosine kinases (dAKs), to sensitize human cancer cells to gemcitabine. Stable and transient transfections of bacterial dNKs into human cells showed that these were much less active than human and fruitfly dNKs. The fusion of dAK from Bacillus cereus to the green fluorescent protein induced a modest sensitization. Apparently, bacterial dNKs did not get properly expressed or are unstable in the mammalian cell.

• Authors: Claire Hébrard, Emeline Cros-Perrial, Anders Ranegaard Clausen, Charles Dumontet, Jure Piskur, Lars Petter Jordheim
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 28 Issue 11 Pg. 1068-75 (Nov 2009) ISSN: 1532-2335 [Electronic] United States
• PMID: 20183574 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Deoxycytidine
• Phosphotransferases (Alcohol Group Acceptor)
• deoxyribonucleoside kinases
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Bacteria (enzymology, genetics)
• Cell Line, Tumor
• Deoxycytidine (analogs & derivatives, pharmacology)
• Genes, Transgenic, Suicide (genetics, physiology)
• Humans
• Inhibitory Concentration 50
• Phosphotransferases (Alcohol Group Acceptor) (genetics, metabolism)
• Transfection
• Gemcitabine