Early temporal changes in the uridine kinase isozyme profile of the novikoff hepatoma in response to 5-azacytidine treatment

Abstract

Using a protocol conductive to the development in vivo of tumor resistance to 5-azacytidine, it is shown that the adult (I) and embryonic (II) forms of uridine kinase in Novikoff ascites tumor cells undergo early transient, but marked increases in activity, before falling below control values. The activities of I and II reversibly increase approximately 2-fold within one and four generations, respectively, from the beginning of treatment, then decline to approximately 30 per cent of the control value by the tenth generation; II predominates between generation two and ten. These early fluctuations in the concentrations of I and II, which probably account in part for the reported initial non-correspondence between uridine kinase activity and degree of resistance to pyrimidine analogs, are relevant to the problem of the development of tumor resistance to pyrimidine analogs.