Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of @entity5 . This may be done by determining the pharmacokinetics of specific substrates. We generated @entity4540 (GCV)-sensitive @entity1 @entity189 cell lines after transfection with a retroviral vector bearing the herpes simplex virus @entity1014 kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (r = 0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the @entity2353 carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the @entity2353 transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.

@entity4540 uptake in XXXX @entity189 cells expressing herpes simplex virus @entity1014 kinase.

@entity1 :: ('9606', 'Species') :: ['human'] @entity2353 :: ('CHEBI:33838', 'Chemical') :: ['nucleoside'] @entity5 :: ('MESH:D009369', 'Disease') :: ['malignant tumors'] @entity189 :: ('MESH:D002277', 'Disease') :: ['mammary carcinoma'] @entity1014 :: ('MESH:D013936', 'Chemical') :: ['thymidine'] @entity4540 :: ('MESH:D015774', 'Chemical') :: ['ganciclovir']
@entity1 :: (9606,Species) :: ['human']
