Antimutagenic activity of fluphenazine in short-term tests

Fluphenazine, an antipsychotic drug that belongs to the phenothiazine famil y, reduced the genotoxicity of standard direct- and indirect-acting mutagen s in the Ames test, both in the presence and in the absence of promutagen-a ctivating So fraction. In short-term tests on human lymphocytes, the inhibi tory effect of fluphenazine on the genotoxicity of standard mutagens was st rongest in the cytokinesis-blocked micronucleus assay and in the thioguanin e-resistance test, and weakest in the sister chromatid exchange test. Fluph enazine also considerably reduced the level of free radicals estimated in i rt vitro samples of human granulocytes. The results suggest that, in the ra nge of the tested concentrations, fluphenazine could be considered for use to prevent the genotoxicity of daunorubicin, methyl methanesulfonate, benzo [a]pyrene and mitomycin C. Reduction in the level of free radicals appears to be an important mechanism of the antimutagenic action of fluphenazine.