In vivo chromosome damaging effects of an inosine monophosphate dehydrogenase inhibitor: Ribavirin in mice

Objective: To investigate the in vivo mutagenic effects of ribavirin in mice. Methods: Mice were injected (i.p.) 20, 100, or 200 mg/kg ribavirin (single exposure) for bone marrow micronucleus, peripheral blood micronucleus and bone marrow chromosome aberration tests. Five treatments of 200 mg/kg ribavirin was given (i.p.) for sperm morphology test. The tests were performed as per the standard procedures. Results: Ribavirin induced significant number of micronucleated polychromatic erythrocytes (MNPCEs) at 24, 48 and 72 h following the exposure with more effects at 24 h (p<0.05-0.001). Micronucleated PCEs were more at 48 h in lower dose-levels and at 72 h in highest dose-level in the peripheral blood (p<0.05-0.001). Ribavirin induced structural chromosomal damage hence producing the fragments for the micronucleus formation. Ribavirin decreased the PCE%, P/N ratio and the mitotic index indicating that it prevents cell division in mouse bone marrow. Ribavirin also decreased the testis weight and induced the formation of abnormal sperms. Conclusion: Ribavirin is a potent mutagen and cytotoxic agent in mice in vivo. Further, it also induces point mutations in germ cells yielding abnormal sperms. The genotoxic effects of ribavirin are not exerted in a dose-dependent pattern in mouse.