Biochemical mechanism of drug resistance—VII: Inhibition of orotic acid metabolism by 5-azacytidine in leukemic mice sensitive and resistant to 5-azacytidine
Application of 5-azacytidine to leukemic AKR mice results in an inhibition of the utilization of orotic acid in the liver. In 5-azacytidine-sensitive animals, the inhibition is greater than in the resistant ones. Similarly, the excretion of orotic acid and orotidine in the urine is higher after appl...
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| Veröffentlicht in: | Biochemical pharmacology 1968-04, Vol.17 (4), p.519-524 |
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| creator | Veselý, J. Čihák, A. Šorm, F. |
| description | Application of 5-azacytidine to leukemic AKR mice results in an inhibition of the utilization of orotic acid in the liver. In 5-azacytidine-sensitive animals, the inhibition is greater than in the resistant ones. Similarly, the excretion of orotic acid and orotidine in the urine is higher after application of 5-azacytidine in the sensitive animals. Cell-free extracts from leukemic cells, both sensitive and resistant to 5-azacytidine, showed a decreased activity of orotidylic acid decarboxylase after application of 5-azacytidine
in vivo. The differences in the metabolism of orotate are related to the decreased ability of 5-azacytidine-resistant leukemic cells to convert 5-azacytidine to 5-azacytidine 5'-phosphate. |
| doi_str_mv | 10.1016/0006-2952(68)90267-0 |
| format | Article |
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| ispartof | Biochemical pharmacology, 1968-04, Vol.17 (4), p.519-524 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Antimetabolites - pharmacology Carbon Isotopes Cell-Free System Depression, Chemical Female Leukemia, Experimental - metabolism Liver - drug effects Liver - metabolism Mice Nucleosides - pharmacology Orotic Acid - metabolism Orotic Acid - urine Phosphates - metabolism RNA - biosynthesis |
| title | Biochemical mechanism of drug resistance—VII: Inhibition of orotic acid metabolism by 5-azacytidine in leukemic mice sensitive and resistant to 5-azacytidine |
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