EVALUATION OF THE GENOTOXIC POTENTIAL OF SELECTED ANTI-AIDS TREATMENTDRUGS AT CLINICAL DOSES IN-VIVO IN MICE

Six anti-AIDS drugs were assessed for in vivo genotoxicity and cytotox icity at human clinical doses with the mouse bone marrow micronucleus assay. These included four dideoxynucleosides (azidothymidine, dideoxy cytidine, dideoxyadenosine, and dideoxyinosine); an anthracycline anti biotic (doxorubicin), and a chelating agent (D-penicillamine). Cytolog ical analysis of the mouse bone marrow cells revealed: (i) The dideoxy nucleosides and D-penicillamine failed to induce significant number of micronuclei, and except for one of the five doses of dideoxyinosine, none of the dideoxynucleosides were cytotoxic at the doses tested. (ii ) Doxorubicin induced micronuclei in a dose-dependent manner which was statistically significant at 4-times the clinical dose but was not cy totoxic at any of the doses tested.