Interaction of iododeoxyuridine and its primary metabolite, iodouracil on radiation response

An in vitro model using Chinese hamster V79 cells was designed to test the interaction of iododeoxyuridine (IdUrd) and its primary metabolite, iodouracil (IU) on growth and radiation response. A recent clinical pharmacology study documented that while steady-state arterial plasma levels of IdUrd remained linear over the dose range of 250-1200 mg/m2/12 hour intravenous infusion, plasma levels of IU rose to greater than 1 log higher (approaching 10(-4) M) at the completion of the 12-hour infusion. Using these clinically relevant doses of IdUrd and IU, we report no apparent effect on radiosensitization of IU alone, or in combination with IdUrd using exponentially growing V79 cells. Similarly, IU does not result in any growth delay. Thus, unlike the recent reports of 5-fluorouracil being incorporated into DNA following phosphorylation to FdUMP, iodouracil does not appear to follow similar metabolic pathways and is unlikely to contribute to the clinical radiosensitizing potential of iododeoxyuridine.