In vitro effects of albendazole and its metabolites on the cell proliferation kinetics and micronuclei frequency of stimulated human lymphocytes

Background. Albendazole (ABZ) is an antiparasitic drug used for the treatme nt of several helminthiases. After its oral administration, this compound i s metabolized to sulfoxide (SOABZ) and sulfone (SO(2)ABZ), SOABZ being the active metabolite, The antiparasitic activity of ABZ has been associated wi th its capacity to bind with tubulin, altering microtubule formation, Altho ugh some studies indicate that ABZ modified microtubule structure in host c ells, data concerning the consequences of this phenomenon in human cells ar e scant, Methods. In this study we evaluated the effects of ABZ and its metabolites on cell proliferation, as well as on the frequency of micronucleated cells in cultured human lymphocytes. Results. ABZ and SOABZ arrested cell proliferation in metaphase and increas ed the frequency of micronuclei in treated lymphocytes. Contrariwise, SO(2) ABZ, the inactive metabolite, did not produce any significant effect, Conclusions. The formation of micronuclei may ultimately result in aneuploi dy induction, an effect that could have severe consequences in humans. Howe ver, the doses of ABZ and SOABZ at which these effects were observed are se veral orders of magnitude higher than those found in the plasma of treated individuals. Because there are other mechanisms by which aneuploidy can be induced at even lower doses than micronuclei, i.e., chromosome nondisjuncti on, it is necessary to evaluate this effect in exposed individuals. (C) 200 1 IMSS, Published by Elsevier Science Inc.