INDUCTION BY COCAINE OF DEFECTIVE SPINDLE FORMATION IN CULTURED MOUSEOOCYTES

The effect of cocaine on spindle morphology in mouse oocytes was inves tigated. Oocytes were exposed to 10, 100 and 1000 mu g cocaine/ml and cultured for 20 hr to the metaphase II equivalent stage. Spindles were visualized in whole-mount preparations by indirect immunofluorescence staining for tubulin. Concentrations of 10 and 100 mu g cocaine/ml ha d no significant effect on oocyte maturation. Cocaine at a concentrati on of 10 mu g/ml also had no discernible effect on spindle morphology but exposure to 100 mu g/ml resulted in a significant increase in the frequency of defective spindles (44 +/- 7% compared with 12 +/- 2% in controls). Exposure to 1000 mu g cocaine/ml blocked development at the metaphase I stage. The abnormal spindles were characterized by barrel shapes and asymmetric spindle halves containing wavy or branched spin dle fibres. Chromosome misalignment was also observed in some cases. S pindle-active agents are known to cause chromosome malsegregation and the results of this study suggest that cocaine may have the potential to cause aneuploidy. Copyright (C) 1996 Elsevier Science Ltd