Effects of 5-aza-2'-deoxycytidine on DNA synthesis in mouse lymphatic tissues

5-Aza-2'-deoxycytidine-3H administered i. p. to mice is preferentially incorporated into nucleic acids in the spleen and thymus. The labeling of the spleen is maximal during first hours after drug administration and decreases rapidly thereafter. Following administration, 5-aza-2'-deoxycytidine is metabolized giving rise to several new compounds. The incorporation of 5-aza-2'-deoxycytidine is blocked by the simultaneously administered deoxycytidine to a lesser degree than that of deoxycytidine by the analogue. Maximal inhibition of deoxycytidine incorporation by the drug was observed in the spleen; the incorporation of thymidine under similar conditions was diminished only about 20%. However, pretreatment of the animals with the analogue resulted in a strong inhibition of thymidine incorporation (about 80%) both in the spleen and the thymus. Simultaneously the activity of thymidine and thymidylate kinases in cell-free spleen extracts was markedly depressed.