[Different susceptibility of cell lines to @entity1014 kinase/ XXXX -mediated killing effect and the way of cell death].

@entity778 @entity39 @entity4 @entity70726 @entity24525 @entity98 @entity1014 @entity4540
OBJECTIVE: To investigate the mechanism of @entity778 (HSV) @entity1014 kinase (TK)/ @entity4540 (GCV)-mediated suicide effect obtained in three different cell lines and the ways in which this system-mediated cell killing occurs. METHODS: Recombinant retroviral vector expressing HSV-TK was transduced into three cell lines known with different growth rate ( @entity70726 and LLC- @entity24525 ). The doubling time of the transduced and parental cells was calculated. @entity98 method was used to detect the concentration of GCV at which cell growth was inhibited by 50% (IC(50) value). Cell cycle was analyzed by flow cytometry. @entity39 or apoptosis of cultured cells and/or xenografts was observed under light and electron microscope, and by in situ apoptosis detection. RESULTS: The doubling time of the three parental cell lines was (31.2 +/- 0.1) h, (48.3 +/- 0.1) h, and (53.9 +/- 0.1) h, separately. The IC(50) values of their HSV-TK-transduced cell lines to GCV were (0.73 +/- 0.12) micromol/L, (0.93 +/- 0.16) micromol/L and (1.22 +/- 0.06) micromol/L, respectively and the IC(50) value was correlated with the cell doubling time. Flow cytometry revealed S arrest. The majority of cells under treatment of GCV displayed @entity4 , but very few cells showed apoptosis. Large areas of @entity39 were observed in the xenografts. CONCLUSIONS: The cells with high growth rate are more susceptible to HSV-TK/GCV-mediated killing effect. @entity39 is the main way in which cells of the three HSV-TK-transduced cells lines die.
