Influence of ribavirin on the micronucleus formation and in vitro proliferation of human lymphocytes

Abstract

Cytotoxic effects of the antiviremic drug ribavirin (1-beta -D-ribofuranosyl-1,2,4-triazole-3-carboxamide) were evaluated in vitro measuring micronucleus formation and cell proliferation kinetics in whole blood cultures employing cytokinesis block (CB) micronucleus test. The cells were exposed to ribavirin doses ranging from 0.05-0.65 mu mol/ml at three different incubation times. The frequency of micronuclei in treated samples demonstrated relatively low ability of ribavirin to induce micronuclei. However, the lowest concentration of ribavirin markedly changed the frequency of mononucleated and multinucleated cells, particularly binucleated ones, which declined significantly. The decline in the frequency of binucleate cells was followed with accumulation of greater number of mononucleate cells. Decreased proliferation potential of lymphocytes treated with ribavirin indicates that cells are arrested prior to metaphase. The present investigation showed that ribavirin is capable to induce a delay in cellular proliferation at all the doses assayed. The study demonstrated that CB micronucleus assay is simple and rapid method that can be used to assess toxic effect of drugs in vitro.