Non-disjunction events induced by albendazole in human cells.
Albendazole (ABZ), a benzimidazole carbamate used for the treatment of several human helminthiases has high affinity for tubulin, which results in an inhibition of microtubule polymerization, blocking several vital processes in the parasites, such as motility and nutrient uptake. The ability of ABZ to act as mitotic spindle poison leads to a potential risk for aneuploidy induction in exposed human beings. ABZ, as well as albendazole sulphoxide (ABZSO), its main metabolite, induce micronuclei in human cells in a dose-dependent manner. Despite recognition that ABZ and ABZSO increase micronucleus frequency, their potential as inducers of non-disjunction in human cells, an event considered more frequent than chromosome loss, and one of the main mechanisms involved in aneuploidy induction, has not been evaluated. In the present work, we investigated the ability of ABZ and ABZSO to induce non-disjunction in cultured human lymphocytes. Non-disjunction was scored by chromosome-specific FISH using a classical or alpha satellite probe for chromosomes 1 and 7, respectively. Significant increase in non-disjunction events that involved either chromosome were observed in cells treated with ABZ or ABZSO. Both ABZ and ABZSO induced non-disjunction at lower concentrations than those at which MN were observed.
Ramírez
Tzutzuy
T
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, México, D.F., Mexico.
Eastmond
David A
DA
Herrera
Luis A
LA
D015766:Albendazole / Q000633:toxicity*; D000871:Anthelmintics / Q000633:toxicity*; D002478:Cells, Cultured; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D009630:Nondisjunction, Genetic / Q000187:drug effects*
D000871:Anthelmintics; D015766:Albendazole