Purine modulation of thymidine activity in L1210 leukemia cells in vitro

Alteration of purine metabolism using adenine was studied in mouse L1210 leukemia cells for its effect on dThd-mediated inhibition of growth and deoxyribonucleotide pool perturbations. Inhibition of cell growth caused by 10 to 50 microM dThd was enhanced more than additively by 100 microM adenine which was only slightly inhibitory when administered alone. Adenine at 100 microM affected ribonucleotide levels by expanding the ATP pool and causing slight decreases in the GTP, UTP and CTP pools, while dThd alone or in combination with adenine had no effect on ribonucleotide pools. dThd at 10 microM caused a more than 2-fold increase in the dTTP pool and a marked but transient decrease in the dCTP pool with lesser effects on purine deoxyribonucleotide levels. Adenine at 100 microM produced only slight, transient increase in the dATP pool. Exposure of cells to dThd plus adenine compared with individual agents produced more than additive increases in dTTP and dATP pools. The decrease in the dCTP level was more with combined agents than with dThd alone. The results showed that an alteration in adenine nucleotide pools modifies the activity of dThd through greater enhancement of dTTP levels leading to a greater suppression of the dCTP pool.