Reduction of Antileukemic and Immunosuppressive Activities of 5-Azacytidine in Mice by Concurrent Treatment with Uridine 1

Abstract

Summary

Investigations were carried out to determine the influence of concurrent treatment with uridine on the antileukemic, toxic, and immunosuppressive effects of 5-AzaCyd, a synthetic analog of cytidine. A single treatment on day 1 after tumor implantation with 5-AzaCyd alone (20–90 mg/kg) increased the MST of leukemic mice by 57–79% over the untreated controls. Combination treatment with uridine reduced the antileukemic activity of 5-AzaCyd. Treatment with 150 or 250 mg/kg of 5-AzaCyd was lethal to leukemic as well as nonleukemic mice. Concurrent treatment with uridine reduced the toxic effect of 5-AzaCyd in these mice.

A single treatment with 5-AzaCyd alone (20–250 mg/kg) diminished the surviving bone marrow cells 30 to 6% and CFU to 2% of the untreated control values. Treatment with uridine reduced the toxic effect of 5-AzaCyd on the bone marrow cells and CFU. Similarly, a single treatment with 5-AzaCyd (33–150 mg/kg) inhibited the hemagglutinin synthesis and hemolytic plaque-forming ability of the spleen cells of nonleukemic mice. In hemagglutination tests simultaneous administration of uridine reduced the immunosuppressive effect of 5-AzaCyd to a greater extent when the drugs were administered after, rather than before, SRBC administration, Furthermore, treatment with uridine partially reversed the effect of 5-AzaCyd on hemolytic plaque-forming cells.