T Ramírez1, L Benítez-Bribiesca, P Ostrosky-Wegman, L A Herrera. 1. Departamento de Genética y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
Abstract
BACKGROUND: Albendazole (ABZ) is an antiparasitic drug used for the treatment of several helminthiases. After its oral administration, this compound is metabolized to sulfoxide (SOABZ) and sulfone (SO(2)ABZ), SOABZ being the active metabolite. The antiparasitic activity of ABZ has been associated with its capacity to bind with tubulin, altering microtubule formation. Although some studies indicate that ABZ modified microtubule structure in host cells, data concerning the consequences of this phenomenon in human cells are 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 increased 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 aneuploidy induction, an effect that could have severe consequences in humans. However, the doses of ABZ and SOABZ at which these effects were observed are several 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 nondisjunction, it is necessary to evaluate this effect in exposed individuals.
BACKGROUND:Albendazole (ABZ) is an antiparasitic drug used for the treatment of several helminthiases. After its oral administration, this compound is metabolized to sulfoxide (SOABZ) and sulfone (SO(2)ABZ), SOABZ being the active metabolite. The antiparasitic activity of ABZ has been associated with its capacity to bind with tubulin, altering microtubule formation. Although some studies indicate that ABZ modified microtubule structure in host cells, data concerning the consequences of this phenomenon in human cells are 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 increased 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 aneuploidy induction, an effect that could have severe consequences in humans. However, the doses of ABZ and SOABZ at which these effects were observed are several 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 nondisjunction, it is necessary to evaluate this effect in exposed individuals.