| Acute cytotoxicity of arabinofuranosyl nucleoside analogs is not dependent on mitochondrial DNA. | |
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MedLine Citation:
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PMID: 19481540 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nucleoside analogs 9-beta-D-arabinofuranosylguanine (araG) and 1-beta-d-arabinofuranosylthymine (araT) are substrates of mitochondrial nucleoside kinases and have previously been shown to be predominantly incorporated into mtDNA of cells, but the pharmacological importance of their accumulation in mtDNA is not known. Here, we examined the role of mtDNA in the response to araG, araT and other anti-cancer and anti-viral agents in a MOLT-4 wild-type (wt) T-lymphoblastoid cell line and its petite mutant MOLT-4 rho(0) cells (lacking mtDNA). The mRNA levels and activities of deoxyguanosine kinase (dGK), deoxycytidine kinase (dCK), thymidine kinase 1 (TK1) and thymidine kinase 2 (TK2) were determined in the two cell lines. Compared to that in the MOLT-4 wt cells the mRNA level of the constitutively expressed TK2 was higher (p<0.01) in the rho(0) cells, whereas the TK1 mRNA level was lower (p<0.05). The enzyme activity of the S-phase restricted TK1 was also lower (p<0.05) in the MOLT-4 rho(0) cells, whereas the activities of dGK, dCK and TK2 were similar in MOLT-4 wt and rho(0) cell lines. The sensitivities to different cytotoxic nucleoside analogs were determined and compared between the two cell lines. Interestingly, we found that the acute cytotoxicity of araG, araT and other anti-viral and anti-cancer agents is independent of the presence of mtDNA in MOLT-4 T-lymphoblastoid cells. |
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Authors:
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Sophie Curbo; Magnus Johansson; Jan Balzarini; Lionel D Lewis; Anna Karlsson |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-28 |
Journal Detail:
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Title: Experimental cell research Volume: 315 ISSN: 1090-2422 ISO Abbreviation: Exp. Cell Res. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-07-31 Completed Date: 2009-09-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 2539-43 Citation Subset: IM |
Affiliation:
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Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. sophie.curbo@ki.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / toxicity* Arabinonucleosides / toxicity* Cell Line, Tumor / drug effects DNA, Mitochondrial / genetics, metabolism* Deoxycytidine Kinase / genetics, metabolism Humans Phosphotransferases (Alcohol Group Acceptor) / genetics, metabolism Thymidine / analogs & derivatives*, toxicity Thymidine Kinase / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Arabinonucleosides; 0/DNA, Mitochondrial; 38819-10-2/9-arabinofuranosylguanine; 50-89-5/Thymidine; 605-23-2/ara-T; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/thymidine kinase 2; EC 2.7.1.113/deoxyguanosine kinase; EC 2.7.1.21/Thymidine Kinase; EC 2.7.1.21/thymidine kinase 1; EC 2.7.1.74/Deoxycytidine Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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