EFFECTS OF (+)-INDENESTROL, (-)-INDENESTROL AND (+/-)-INDENESTROLS A AND B ON MICROTUBULE DISTRIBUTION AND CYTOTOXICITY IN CHINESE-HAMSTER V79 CELLS

We have reported that (+)-, (-)- and (+/-)-indenestrols A and B (IA and IB respectively) inhibit the polymerization of microtubule proteins isolated from porcine brain in vitro. In this study, the effects of (+)-, (-)- and (+/-)-IA and IB on the relative plating efficiency, chromosome number and cellular microtubular architecture of Chinese hamster V79 cells, detected with a fluorescent anti-tubulin antibody, were investigated. The results indicated that the effect of (+/-)-IA was similar to that of diethylstilbestrol and that of (+/-)-IB was greater than that of (+/-)-IA. We also-determined the effects of the optically active IA and IB isomers and found that the rank order of cytotoxic activity of the IA and IB series was: (-)-IA > (+/-)-IA > (+)-IA and (+/-)-IB greater-than-or-equal-to (-)-IB > (+)-IB. Furthermore, we studied the intracellular disturbance of microtubule formation induced by these compounds and found that (-)-IA had by far the greatest disruptive effect.