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Biochemical changes associated with the development of resistance to 5‐azacytidine in AKR leukemic mice
Author(s) -
Veselý J.,
Seifert J.,
Čihák A.,
Šorm F.
Publication year - 1966
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.2910010106
Subject(s) - cytidine , uridine , orotic acid , thymidine , azacitidine , biology , guanosine , leukemia , biochemistry , thymidine kinase , in vivo , microbiology and biotechnology , in vitro , rna , enzyme , immunology , gene expression , virus , dna methylation , herpes simplex virus , gene
Resistance to 5‐azacytidine, a potent inhibitor of the growth of mouse lympaoid leukemia cells in vivo , was achieved in an inbred strain of AKR mice in the third transplant period. The incorporation of orotic acid into the livers of such resistant mice was more than six times lower than in animals carrying the 5‐azacytidine‐sensitive parent strain of leukemia. The incorporation of orotic acid by 5‐azacytidine‐sensitive mice was inhibited by 5‐azacytidine twice as much as in 5‐azacytidine‐resistant animals. The incorporation of uridine, cytidine, thymidine, deoxycytidine, and of guanosine into nucleic acids was also significantly depressed in 5‐azacytidine‐resistant leukemic cells. Uridine kinase activity was decreased by 20%, while uridine phosphorylase activity was diminished by 31–50%. The resistant leukemic mice were cross‐resistant to 5‐fluorouracil; in contrast, however, their sensitivity to aminopterin was increased significantly.