ABSTRACT
Cellular uptake and metabolism are dependent on the TdR salvage pathway, where they undergo initial intracellular phosphorylation to the monophosphate derivative (BdUMP, IdUMP) by the rate-limiting enzyme, thymidine kinase (Figure 4.3). Sequential phosphorylation to triphosphates (BdUTP, IdUTP) results in the use of the modied analogues during scheduled (S-phase) and unscheduled DNA synthesis, in competition with deoxythymidine triphosphase (dTTP) by DNA polymerase. DNA incorporation is a prerequisite for radiosensitization in human tumors as well as in normal cells, and the extent of radiosensitization correlates directly with the percentage of TdR replacement in DNA [1].
