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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.
Insights
Ribavirin demonstrated toxicity to hematopoietic stem cells in mice, reducing key cell populations. Its effects on Friend virus infection suggest cytotoxicity rather than a specific antiviral mechanism.
Area of Science:
- Hematology
- Virology
- Pharmacology
Background:
- Ribavirin is an antiviral medication.
- Friend virus infection in mice causes polycythemia and a specific CFU-E population (CFU-EI).
- CFU-EI cells are erythropoietin-independent and serve as a disease marker.
Purpose of the Study:
- To investigate the toxic effects of ribavirin on hematopoietic stem cells.
- To evaluate ribavirin's impact on Friend virus infection and related cell populations.
- To determine if ribavirin's effects are cytotoxic or antiviral.
Main Methods:
- Administered ribavirin to normal and Friend virus-infected mice.
- Quantified hematopoietic stem cells (CFU-S, CFU-C, CFU-E) using in vitro techniques.
- Assessed spleen weight and CFU-EI population as indicators of disease progression.
- Tested ribavirin's effect on CFU-E and CFU-EI in vitro.
- Studied ribavirin's effect in mice pretreated with hydroxyurea.
Main Results:
- Ribavirin reduced hematopoietic stem cells (CFU-S, CFU-C, CFU-E) in normal mice.
- In Friend virus-infected mice, ribavirin delayed spleen weight increase and the transformation of CFU-E to CFU-EI.
- Ribavirin inhibited CFU-E and CFU-EI in vitro at similar concentrations.
- Ribavirin delayed Friend leukemia recurrence in hydroxyurea-pretreated mice, but CFU-E remained predominantly Ep-independent.
Conclusions:
- Ribavirin exhibits cytotoxic effects on hematopoietic stem cells.
- The observed effects of ribavirin in Friend virus infection are attributed to cytotoxicity, not a specific antiviral action.
- Ribavirin's impact on CFU-EI suggests a broader effect on cell proliferation rather than a targeted antiviral response.