Biomaterial Database

Effects of 3'-azido-3'-deoxythymidine on the deoxynucleotide triphosphate pools of cultured human cells. 1988

L W Frick, and D J Nelson, and M H St Clair, and P A Furman, and T A Krenitsky

Department of Experiment Therapy, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.

The effects of 3'-azido-3'-deoxythymidine (AZT) on the deoxynucleotide pools of three human cell lines, HL-60, H-9, and K-562, were determined. The corresponding ED50s for inhibition of cell growth were 670, 100, and 100 microM AZT. In all three lines, exposure to 200 microM AZT caused dTTP and dGTP initially to fall and then to return towards control levels. In contrast to a previous report [Furman et al., (1986) Proc. Nat. Acad. Sci. USA 83, 8333-8337], dCTP levels increased. Pools of dATP were relatively unchanged. Qualitatively similar changes occurred in 10 microM AZT, but recovery was faster than at 200 microM AZT. After 24 hrs incubation with 200 microM AZT, AZT-5'-MP reached 2.8, 4.7, and 15.7 mM in the HL-60, H-9, and K-562 cells, respectively. When HL-60 and K-562 cells incubated in AZT were resuspended in fresh medium, AZT-5'-MP pools declined with respective t1/2 values equal to 34 and 68 min. The concentration of thymidine, and to a lesser extent deoxyuridine, increased in the media of treated cells. AZT-5'-MP was found in the media of cells treated with AZT.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007938	Leukemia	A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)	Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003854	Deoxyribonucleotides	A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.	Deoxyribonucleotide
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998	Antiviral Agents	Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.	Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013936	Thymidine	A nucleoside in which THYMINE is linked to DEOXYRIBOSE.	2'-Deoxythymidine,Deoxythymidine,2' Deoxythymidine
D015215	Zidovudine	A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.	AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U