A Simple Method for Long-Term Drug Infusion in Mice: Evaluation of Guanazole as a Model 1

Abstract

Summary

A simplified technique for iv infusion in unrestricted DBA/2J inbred mice has been described. The method, which involves direct cannulation of the tail vein with polyethylene tubing, is suitable for routine use. Guanazole, an antileukemic agent with a short plamsa half-life, was evaluated as a model compound. After administration for 47 hr at the rate of 0.3 ml/hr, guanazole (30 mg/ml) caused a marked inhibition of incorporation of ¹⁴C-uridine, administered 15 min before sacrifice, primarily into DNA of spleen, thymus and bone marrow in decreasing order. Inhibition of incorporation into RNA was less marked but followed a similar pattern. The effects on the incorporation of uridine in nucleic acids of kidney, heart and brain were minimal. Increased incorporations into RNA and DNA occurred in liver. The data for the hemopoietic and lymphoid organs, namely, spleen, thymus and marrow, are consistent with the reported immunosup-pressive and myelosuppressive effects of the drug and also with the inhibition of ribo-nucleoside diphosphate reducaste by guana-zole.