Toxicity of S-Triazin-2-(1-H)-1, 4-Amino-1-B-D-Ribofuranosyl-5-Azacytidine (NSC 102816)-Clinical Formulation in Mice and Rats Administered a Single Dose by the Intravenous Route. (A Comparison with I.P. and P.O. Toxicity).

摘要

The cancer chemotherapeutic agent, S-triazin-2(1-H)-1,4-amino-1-beta-D-ribofuranosyl-5-azacytidine (NSC 102816),clinical formulation,was administered as a single intravenous injection to Swiss mice weighing 19-28 gma. and Sprague-Dawley rats with body weights of 90-145gms. Single-dose intravenous LD50values calculated Day 29were 117.2 (107.7-127.6) mg/kg and 51.4 (48.9-54.0) mg/kg for the mouse and rat,respectively. The mean day of death in mice was Day 6,and about Day 3in rats. Microscopic examination of tissues from representative animals sacrificed 29days after injection with the drug disclosed an increased degree of extramedullary hematopoiesis in the spleens of 15of 28treated mice. An increased amount of hepatic neutral lipid was detected in 11of 15rats treated at dosage levels >or = 51.7mg/kg. A comparison of data from the present studies with that from earlier single-and repeated-dose oral and intraperitoneal studies in mice,which also showed delayed deaths,revealed that a single-dose of NSC 102816,administered to mice by the intraperitoneal or intravenous route appeared to be about four to five times as toxic as when given orally.