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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
Author(s) -
Veselý J.,
Čihák A.,
Šorm F.
Publication year - 1967
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910020625
Subject(s) - cytidine , uridine , anabolism , deoxycytidine kinase , metabolism , pyrimidine analogue , in vivo , pyrimidine metabolism , in vitro , enzyme , pyrimidine , pharmacology , biochemistry , endocrinology , deoxycytidine , chemistry , biology , medicine , rna , chemotherapy , gemcitabine , genetics , purine , gene
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 affect 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.