Mutagenesis, Vol. 16, No. 1, 31-38,
January 2001
© 2001 UK Environmental Mutagen Society/Oxford University Press
Antimutagenic activity of fluphenazine in short-term tests
siorowski1,3
1 Department of Basic Medical Sciences, Wroc
aw Medical University, 4 Kochanowskiego Str., 51-601 Wrocaw and
2 Psychiatric Clinic, Wrocaw Medical University, 25 Kraszewskiego Str., 50-229 Wrocaw, Poland
Fluphenazine, an antipsychotic drug that belongs to the phenothiazine family, reduced the genotoxicity of standard direct- and indirect-acting mutagens in the Ames test, both in the presence and in the absence of promutagen-activating S9 fraction. In short-term tests on human lymphocytes, the inhibitory effect of fluphenazine on the genotoxicity of standard mutagens was strongest in the cytokinesis-blocked micronucleus assay and in the thioguanine-resistance test, and weakest in the sister chromatid exchange test. Fluphenazine also considerably reduced the level of free radicals estimated in in vitro samples of human granulocytes. The results suggest that, in the range 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.
3 To whom correspondence should be addressed. Fax: +48 71 3479211; Email: kaz{at}basmed.am.wroc.pl