Abstract
Blood of normal and leukemic and bone marrow aspirates of leukemic human subjects were incubated in Eagle's basal medium containing tritiated ara C in the presence and absence of tetrahydrouridine (THU). Nucleosides and nucleotides in acid soluble extracts were fractionated with anionic exchange columns. Nucleotide fractions were also hydrolysed to nucleosides for analysis of deaminated products. Deamination was negligible in normal blood whereas leukemic blood and marrow samples deaminated ara C to a variable extent. Deamination of ara C was inhibited by THU. Relatively little radioactivity was found in mono and di phosphate nucleotide fractions; the levels were not appreciably affected by THU. Among the various leukemic samples and normal blood studied, only acute myelocytic and myelomonocytic leukemia (AML and AMML) showed increased (1.5 to 5 fold) levels of triphosphate nucleotide in the presence of THU. The radioactivity in the triphosphate fractions contained over 90% ara CTP. These results indicate that in AML and AMML the presence of THU can induce net increases in the accumulation of the active metabolite, ara CTP, and suggest the possibility that the combined use of THU and ara C might have increased anti leukemic efficacy in these types of leukemia.
| Original language | English |
|---|---|
| Pages (from-to) | no.313 |
| Journal | Proceedings of the American Association for Cancer Research |
| Volume | 16 |
| Issue number | 66 |
| State | Published - 1975 |
| Externally published | Yes |