Effects of ribavirin on the development of the Friend leukemia

Abstract

Ribavirin (300 and 250 mg/kg i.p., respectively) had a toxic effect on hemopoietic stem cells in normal mice CFU-S, CFU-C, and especially CFU-E were reduced after a single treatment. The drug was further studied in mice infected with the polycythemia-inducing strain of the Friend virus (FV-P). In these mice a specific erythropoietin-independent CFU-E population (CFU-EI) replaces the normal erythropoiesis and can be considered a tumor cell population. With the in vitro technique for CFU-E, CFU-EI can easily be quantified and used as a sensitive marker for the development of the disease. Repeated doses of ribavirin reduced the increase of spleen weight after FV-P infection and the progressive transformation of normal CFU-E into CFU-EI was delayed. The further development of the disease remained unaltered. In vitro CFU-E and CFU-EI were inhibited at the same concentrations when the drug was added to the culture medium. In mice pretreated with multiple doses of hydroxyurea, ribavirin delayed the recurrence of Friend leukemia as seen from the spleen weight increase, but the CFU-E population was predominantly Ep-independent. It is concluded that the effects of the drug were due to its cytotoxicity rather than to a specific antiviral effect.