2'-Deoxycytidine hydrochloride protection of mice against the lethal toxicity of cytosine arabinoside. Absence of protection of bone marrow lymphocytes.

Abstract

Normal mice and mice with advanced leukemia were injected IP with cytosine arabinoside (araC) on a lethal treatment schedule. The simultaneous oral administration of deoxycytidine (CdR) in dose 2–3 times as high as those of araC prevented drug-related death of the animals. Although CdR protected myelo-and erythropoiesis in the bone marrow of normal mice treated with araC, it did not influence the suppression of bone marrow lymphopoiesis. However, in mice treated with araC+CdR, the peripheral blood levels of both lymphocytes and granulocytes were significantly higher than those in animals given araC only. AraC lowered the level of serum hemagglutinins in mice immunized with sheep red blood cells (SRBC), and prolonged skin allograft survival. CdR appeared to normalize only the cellular immune response. In mice with advanced L1210 lymphoblastic leukemia treated with araC+CdR, the effect of the metabolite was selective, i.e., CdR administration led to a complete abrogation of drug-induced lethality without interfering with the highly efficient therapeutic effect of araC. No antitumor effect of araC was shown in araC+CdR-treated mice with advanced granulocytic Graffi leukemia and erythroblastic Rauscher leukemia. We suppose that the combined effect of araC and CdR, araC being administered on a lethal treatment schedule, results in selective destruction of precursor cells with the emphasis on B lymphocytes.