Further study of the mechanism underlying the cellular resistance to AZT

Biochemical and Biophysical Research Communications
Ombretta TurrizianiF Dianzani

Abstract

It has previously been shown that the lymphoblastoid cell line CEM, when propagated in the presence of increasing concentrations of 3'-azido-3'-deoxythymidine, became defective in thymidine kinase activity and resistant to the cytostatic and antiviral activities of AZT. Here we describe the characterization of this cell line (CEMAZT), which revealed that: (i) the defect in TK activity is stable; (ii) TK specific mRNA levels are lower than in the parental line; (iii) the defect of TK activity may be sufficient to produce a lower amount of AZTDP, independently of the activity of thymidylate kinase which does not seem to be defective. Taken together these findings indicate that in CEMAZT the lack of inhibition by AZT may depend only on the defect of TK activity. Also, in preliminary studies of lymphocytes from AZT-treated and untreated patients we observed a metabolic behaviour comparable to that described for CEMAZT and CEM cells.

Citations

Oct 28, 2006·AIDS Research and Human Retroviruses·Ombretta TurrizianiGuido Antonelli
Mar 30, 2002·Alcoholism, Clinical and Experimental Research·Om PrakashSteve Nelson
Apr 1, 2008·Journal of Photochemistry and Photobiology. B, Biology·J F NeaultH A Tajmir-Riahi
Jun 28, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C AlexakisP Kern
Jun 13, 2009·Stem Cells·Robin K SudaRobert J Pignolo

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