DISRUPTION OF MICROTUBULE ASSEMBLY AND SPINDLE FORMATION AS A MECHANISM FOR THE INDUCTION OF ANEUPLOID CELLS BY SODIUM ARSENITE AND VANADIUM PENTOXIDE

Arsenic and vanadium are important environmental and industrial pollut ants. Due to their widespread occurrence and potential genotoxicity, w e studied the aneuploidy-inducing effects of these elements in culture d human lymphocytes using a variety of techniques including fluorescen ce in situ hybridization (FISH) with DNA probes for chromosomes 1 and 7, immunostaining of the lymphocyte spindle apparatus, and an in vitro assay measuring the polymerization and depolymerization of tubulin. D ose-related increases in hyperdiploidy were seen in lymphocyte culture s treated with sodium arsenite (NaAsO2) or vanadium pentoxide (V2O5) o ver concentrations ranging from 0.001 to 0.1 mu M. NaAsO2-treated cell s from different donors exhibited similar hyperdiploid frequencies, wh ereas substantial inter-individual variability was seen in the V2O5-tr eated cells. Examination of the spindle apparatus using an anti-beta-t ubulin antibody indicated that these compounds might disrupt spindle f ormation by interacting with microtubules. Additional in vitro assays using purified tubulin indicated that both compounds inhibited microtu bule assembly and induced tubulin depolymerization. These results indi cate that in vitro exposure to both NaAsO2 and V2O5 can induce aneuplo idy in human lymphocytes, and that this effect may occur through a dis ruption of microtubule function.