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Metabolic properties of an azaguanine-resistant variant of Chinese hamster ovary cells (azarts) with normal levels of hypoxanthine-guanine phosphoribosyltransferase activity

✍ Scribed by Peter G. W. Plagemann; Robert M. Wohlhueter


Publisher
John Wiley and Sons
Year
1985
Tongue
English
Weight
753 KB
Volume
27
Category
Article
ISSN
0730-2312

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✦ Synopsis


Aza'ts 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 6mercaptopurine than wild-type cells. Resistance correlated with a failure of aza'ts 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 aza'ts 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 aza'ts cells and there was no significant degradation of 8-azaguanine or azaguanine nucleotides. We conclude therefore that in aza'ts cells the phosphoribosylation of 8-azaguanine per se is specifically blocked but that this effect is abolished upon cell lysis.