Depression of DNA synthesis in mouse spleen after treatment with 5-aza-2'-deoxycytidine.

5-Aza-2'-deoxycytidine is a highly effective cytostatic agent that preferentially affects the lymphatic system. Pretreatment of noninbred H mice with the drug markedly depressed the level of thymidine (dThd) incorporation into DNA in the spleen and also lowered the dThd and thymidylate kinase activities. Maximum effects were observed following administration of the analog in a single dose 24 hours before the mice were killed. Whereas cytidine and dThd did not reverse the inhibitory effect of 5-aza-2'-deoxycytidine, excessive doses of deoxycytidine partially reversed this inhibition. Similar to the depression of dThd incorporation, a depression in the incorporation of deoxycytidine and cytidine into spleen DNA was found after 24-hour pretreatment with 5-aza-2'-deoxycytidine. However, 7 days following 5-aza-2'-deoxycytidine treatment, the incorporation of dThd into DNA in the spleens of mice was significantly increased. [3H]5-aza-2'-deoxycytidine was rapidly incorporated into spleen DNA, whereas deoxycytidine interfered with the incorporation of [3H]5-aza-2'-deoxycytidine.