EFFECT OF THYMIDINE ON THE SENSITIVITY OF CULTURED MOUSE TUMOR-CELLS TO 1-BETA-D-ARABINOFURANOSYLCYTOSINE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (2) , 538-541
Abstract
Assays of 13 cell lines, derived from mouse lymphomas, myelomas, myeloid tumors, and a mastocytoma, for sensitivity to growth inhibition by 1-.beta.-D-arabinofuranosylcytosine (ara-C) revealed a spectrum between the most and least sensitive which differed 100-fold from each other. An inverse correlation between sensitivity and cellular dCTP content was found. Sensitivity of cells might be increased if the dCTP content was found. Sensitivity of cells might be increased if the dCTP content was lowered during cell exposure to ara-C. Thymidine treatment of cells lowers their dCTP content, and the effect of thymidine on the sensitivity of 6 of the cell lines to ara-C was measured. Concentrations of thymidine below those inhibitory to cell growth by themselves caused an increase in ara-C sensitivity by up to 3-fold in 4 cell lines in which thymidine causes a depression in dCTP content but not in 2 myeloid lines in which the dCTP content was found not to be depressed by the same thymidine treatment. dCTP plays an important role in determining cellular sensitivity to ara-C. The sensitivity of 2 lymphoma cell lines to ara-C could be increased by concentrations of thymidine in the region of 10 .mu.M, which are attainable clinically in humans. A combination of ara-C with thymidine might be useful in the treatment of some human tumors.