A lymphoblastoid cell line, CEM, was rendered resistant to zidovudine (AZT) in vitro by exposure to low but gradually increasing concentrations of the drug. This type of cellular resistance seems to be due to a defect of thymidine kinase (TK) activity that is acquired by cells grown in the presence of AZT: In fact, enzymatic studies with extracts from AZT-resistant cells (CEMazt), have shown that the value of the maximum velocity (Vmax) of TK activity measured with AZT and for deoxythymidine (dThd) is decreased as compared to sensitive CEM cells. Further-move, the enzyme affinity for AZT and dThd is reduced in CEMazt. Further experiments have shown that such cells do not show resistance to other nucleoside analogs, such as ddI, ddC: AraT and D4T, suggesting that the phosphorylation pathways different fr om those involving TK are unaltered. Ex vivo experiments performed by using peripheral blood mononuclear cells (PBMC) from HN infected individuals revealed that a prolonged treatment with AZT may modify the affinity of TK for dThd thus suggesting that the aforementioned phenomenon may occur also in vivo.
Alteration of thymidine kinase activity in cells treated with an antiviral agent / Turriziani, Ombretta; Antonelli, Guido; A., Verri; V., Tozzi; F., Ferri; E., Riva; F., Bambacioni; F., Dianzani. - In: JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS. - ISSN 0393-974X. - STAMPA. - 9:2(1995), pp. 47-51.
Alteration of thymidine kinase activity in cells treated with an antiviral agent
TURRIZIANI, Ombretta;ANTONELLI, Guido;
1995
Abstract
A lymphoblastoid cell line, CEM, was rendered resistant to zidovudine (AZT) in vitro by exposure to low but gradually increasing concentrations of the drug. This type of cellular resistance seems to be due to a defect of thymidine kinase (TK) activity that is acquired by cells grown in the presence of AZT: In fact, enzymatic studies with extracts from AZT-resistant cells (CEMazt), have shown that the value of the maximum velocity (Vmax) of TK activity measured with AZT and for deoxythymidine (dThd) is decreased as compared to sensitive CEM cells. Further-move, the enzyme affinity for AZT and dThd is reduced in CEMazt. Further experiments have shown that such cells do not show resistance to other nucleoside analogs, such as ddI, ddC: AraT and D4T, suggesting that the phosphorylation pathways different fr om those involving TK are unaltered. Ex vivo experiments performed by using peripheral blood mononuclear cells (PBMC) from HN infected individuals revealed that a prolonged treatment with AZT may modify the affinity of TK for dThd thus suggesting that the aforementioned phenomenon may occur also in vivo.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.