L. Bennett, L. Simpson, J. Golden
Oct 1, 1963
Citations
2
Influential Citations
36
Citations
Quality indicators
Journal
Cancer research
Abstract
The effects of 6-mercaptopurine on the incorporation of a number of C14-labeled precursors into soluble purines and into purines of DNA and of RNA have been studied in leukemia L1210 cells, Ehrlich ascites cells, and solid Sarcoma 180, with the purpose of determining which of the several sites at which 6-mercaptopurine may inhibit the biosynthesis of purine nucleotides is the most sensitive in the intact cell in vivo . 6-Mercaptopurine inhibited markedly the incorporation of formate and glycine and did not inhibit the utilization of adenine or 2,6-diaminopurine. There was no inhibition of the incorporation of 4-amino-5-imidazolecarboxamide into adenine derivatives and no consistent and marked inhibition of incorporation into guanine derivatives. In the ascites cell lines, the conversion of 4-amino-5-imidazolecarboxamide to purines was essentially uninhibited by levels of 6-mercaptopurine 8–20 times those that produced a 50 per cent or greater inhibition of synthesis de novo . These results suggest that, in these tumor systems in vivo , the principal site at which 6-mercaptopurine inhibits biosynthesis of purines is at a point prior to the formation of the ribonucleotide of 4-aminoimidazole-5-carboxamide and that the interconversion of purine ribonucleotides is not a primary site of action.