Modulation of deoxycytidine metabolism in vivo with high-dose thymidine in mice

The question of whether selective biochemical modulation of deoxycytidine (dCyd) metabolism by thymidine (dThd) could be quantitated in vivo was addressed. Plasma clearance of [5-3H]dCyd was altered significantly by prior administration (2 hr) of dThd (3,600 mg/kg). The plasma half-life (beta-phase) of [5-3H]dCyd was raised approximately fourfold by dThd. Although dThd consistently caused an increase in the [5-3H]dCyd incorporated into the DNA of the spleen, duodenum, and femur marrow, there was no clear-cut difference between normal (BALB/c X DBA/2)F1 mice and L1210 tumor-bearing (BALB/c X DBA/2)F1 mice that could be translated into a selective advantage. Analysis of tritiated nucleotides in the spleens of normal and L1210 tumor-bearing mice indicated a greater incorporation of [5-3H]dCyd into the dCyd nucleotide pools of L1210 tumor-bearing mice than of normal mice. An analysis with the use of the proportionality constant kappa representing the combined effects of transport, pool sizes, and metabolic incorporation of [5-3H]dCyd into DNA showed that kappa decreased in each organ studied after dThd administration.