Abstract

6-Chloropurine and 6-chloropurine ribonucleoside both inhibited the incorporation of glycine-2-C¹⁴ into polynucleotide guanine without decreasing the rate of incorporation into adenine compounds of sarcoma 180 ascites cells. On a molar basis, the ribonucleoside was more active. Treatment with either drug caused a similar increase in the conversion of adenine-8-C¹⁴ or guanine-8-C¹⁴ to polynucleotide guanine. 6-Chloro-9-ethylpurine was relatively inactive; neither inhibition of labeled glycine into guanine nucleotides nor stimulation of preformed purine utilization for polynucleotide synthesis was observed after treatment with this agent.

6-Chloropurine ribonucleoside and 6-chloro-9-ethylpurine were ineffective inhibitors of the growth of sarcoma 180. These results are similar to past observations obtained with chloropurine. 6-Chloro-9-ethylpurine was relatively inactive in its ability to enhance the carcinostatic properties of azaserine, a previously demonstrated property of chloropurine. Chloropurine ribonucleoside reversed the carcinostatic action of azaserine and markedly decreased the effectiveness of a combination of chloropurine and azaserine. The results of these studies are discussed in relation to the biochemical mechanisms responsible for the drug synergy exhibited by combinations of chloropurine and azaserine.