Metabolic properties of an azaguanine-resistant variant of Chinese hamster ovary cells (azarts) with normal levels of hypoxanthine-guanine phosphoribosyltransferase activity.
Azarts Chinese hamster ovary cells were 20 to 50 times more resistant to 8-azaguanine and 50 to 10 times more resistant to both 6-thioguanine and 6-mercaptopurine than wild-type cells. Resistance correlated with a failure of azarts cells to incorporate 8-azaguanine into the nucleotide pool and into nucleic acids. The uptake of hypoxanthine and guanine, on the other hand, was about the same in both types of cells and the hypoxanthine-guanine phosphoribosyltransferase of the azarts cells as measured in cell lysates was unaltered both in concentration and kinetic properties with hypoxanthine as well as 8-azaguanine as substrate. Plasma membrane permeability to 8-azaguanine and the regulation of intracellular pH were also not altered in azarts cells and there was no significant degradation of 8-azaguanine or azaguanine nucleotides. We conclude therefore that in azarts cells the phosphoribosylation of 8-azaguanine per se is specifically blocked but that this effect is abolished upon cell lysis.
D000818:Animals; D001375:Azaguanine / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D005260:Female; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D007042:Hypoxanthines / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism
D007042:Hypoxanthines; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase; D001375:Azaguanine