Thymidine kinase system

A promising approach is the monoclonal antibody conjugate targeted PDT such as conjugates to anti-EGF or conjugates to anti-transferrin receptor [85,86] or the targeted therapy against the thymidin kinase system [6]. 

In a study using cultured L5178Y mouse lymphoma cells, Rogers and Back (1981) reported that both 1,1-dimethylhydrazine and 1,2-dimethylhydrazine induced forward mutations at the thymidine kinase level in the absence of an extraneous metabolic activation system. The investigators also noted that the two dimethylhydrazines appeared to have different modes of action under these conditions. 

Yet another strategy that may prove useful is the introduction into tumour cells of a sensitivity gene. This concept dictates that the gene product should harbour the ability to convert a non-toxic pro-drug into a toxic substance within the cells - thus leading to their selective destruction. The model system most used to appraise such an approach entails the use of the thymidine kinase gene of the herpes simplex virus (Figure 14.12). 

Clive, D., Flamm, W.G. and Patterson, J.B. (1972). A mutational assay system using the thymidine kinase locus in mouse lymphoma cells. Mutation Res. 16 77-87. 

Other research groups are combining stress inducible promoters with the Cre-LoxP site specific recombination system of PI bacteriophage. Scott et al. (2000) have combined the ionizing radiation inducible EGR-1 promoter with this recombination system to express herpes simplex vims thymidine kinase (HSV-tk). With this combination system, radiation doses relevant for cancer treatment can be used to... 

Fillat, C., Carrio, M., Cascante, A., and Sangro, B. Suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene/ganciclovir system Fifteen years of application. Curr. Gene. Ther. 3 13-26, 2003. 

Penciclovir triphosphate has lower affinity for the viral DNA polymerase than acyclovir triphosphate, but it achieves higher intracellular concentrations and has a more prolonged intracellular effect in experimental systems. The most commonly encountered clinical mutants of HSV are thymidine kinase-deficient and are cross-resistant to acyclovir and famciclovir. 

One system uses mouse lymphoma cells and detects mutations that cause deficiency of thymidine kinase (TK). Another uses Chinese hamster cells and detects mutations in the gene that produces hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Both tests cure efficient, are widely applied, and can be completed in a few weeks. Although not as simple, rapid, and efficient as the Salmonella tests, they have the advantage of being done in a eukaryote. Mammalian-cell cultures cure also used to test for chromosomal mutation. 

Nannalian cells Mutation Mouse lymphoma L5178Y cells Thymidine kinase (TK) system... 

Voges, J., Weber, F., Reszka, R., Sturm, V., Jacobs, A., Heiss, W. D., Wiestler, O., and Kapp, J. F. (2002), Clinical protocol Liposomal gene therapy with the herpes simplex thymidine kinase gene/ganciclovir system for the treatment of glioblastoma multiforme, Hum. Gene Ther., 13, 675-685. 

B. Moss, Vaccinia vims expression vector a new tool for immunologists, Immunology Today, 6, 1985, 243-5 J. A. McCart et al., Systemic cancer therapy with a tumor-selective vaccinia vims mutant lacking thymidine kinase and vaccinia growth factor, Cancer Research, 61, 2001, 8751-7. 

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