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Biochemical mechanisms of drug resistance IV. Development of resistance to 5-azacytidine and simultaneous depression of pyrimidine metabolism in leukemic mice

✍ Scribed by J. Veselý; A. Čihák; F. Šorm

Publisher
John Wiley and Sons
Year
1967
Tongue
French
Weight
547 KB
Volume
2
Category
Article
ISSN
0020-7136

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✦ Synopsis

The development of resistance of leukemic AKR mice to 5-azacytidine administered in small doses was investigated. The activity of uridine kinase decreased simultaneously with the development of resistance. The gradual shortening of the survival time of treated animals and the depression of enzyme activity had a continuous character. The application of 5-azacytidine along with hydrocortisone or actinomycin D did not appreciably afect the development of resistance. In leukemic cells resistant to 5-azacytidine the incorporation of uridine, cytidine and 5-azacytidine itself into ribonucleic acids was depressed in accordance with the impaired anabolic transformations of 5-azacytidine in vivo as well as with the soluble fraction in vitro.

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## Abstract Partially purified uridine kinases from 5‐azacytidine‐sensitive and ‐resistant leukemic cells of AKR mice were separated on a Sephadex G‐200 column. The elution profile of both enzymes was similar although specific activity of uridine kinase from 5‐azacytidine‐resistant cells was more t