THE METABOLISM OF 2,6-DIAMINOPURINE BY DIAMINOPURINE-SENSITIVE AND DIAMINOPURINE-RESISTANT L-STRAIN MOUSE FIBROBLASTS

Abstract

Mouse fibroblasts (strain L) resistant to growth inhibition by 2,6-diaminopurine (DAP) were obtained from DAP-sensitive cultures. DAP-resistant cells were characterized by (a) stability of resistance in the absence of DAP, (b) cross resistance to 8-azaadenine, (c) very limited utilization of C14-labelled DAP or adenine for the synthesis of nucleic acid purines, and (d) greatly decreased adenylic acid and DAP ribonucleotide pyrophosphorylase activities. The base ratios for ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) of DAP-resistant cells did not differ significantly from the corresponding ratios for DAP-sensitive cells.The metabolism of DAP by L-cells was found to be similar to the metabolism of the compound by rodent tissues in vivo. In the presence of low concentrations of DAP-2-C14, DAP-sensitive L-cells readily utilized DAP for the synthesis of acid-soluble derivatives and nucleic acid purines, especially guanine. At low concentrations of DAP-2-C14the utilization of DAP-2-C14by DAP-resistant and DAP-sensitive cells increased with the concentration of DAP-2-C14, but the utilization of DAP-2-C14by DAP-resistant cells increased at a very much lower rate than the utilization of the analogue by DAP-sensitive cells. Adenine-C14was utilized more extensively than DAP-2-C14for the synthesis of nucleic acids of DAP-resistant cells. No correlation between the intracellular concentration of any acid-soluble derivative of DAP and inhibition of cell growth was found.