Molecular Pharmacology, Vol 12, 177-184, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Growth Rate and Deoxynucleoside Triphosphate Concentrations in Cultured Leukemia L1210 Cells

¹ Roswell Park Memorial Institute, James T. Grace Cancer Drug Center, Buffalo, New York 14263

Thymidine and deoxyguanosine produce antiproliferative effects on murine Leukemia L1210 cells when added to the growth medium, and these effects can be prevented by the addition of one on a combination of deoxynucleosides. This study utilized these toxic deoxynucleosides to induce growth rate inhibition in L1210 cells in order to investigate the relationship between growth rate and deoxynucleoside triphosphate pool size in mammalian cells. Deoxyguanosine toxicity of these cells was manifested by deoxynucleoside triphosphate concentration changes which were correlated with growth rate. Both dTTP and dCTP decreased in parallel in a linear manner, while dATP remained unaffected and dGTP increased. In thymidine-inhibited cells, although both dCTP and dATP decreased, only their sum diminished in proportion to growth inhibition.