Oda T, Sakakibara Y, Ichinoseki K, Aizu-Yokota E, Sato Y
Division of Biochemistry, Kyoritsu College of Pharmacy, Tokyo, Japan.
Mutat Res. 1993 Oct;289(2):223-30. doi: 10.1016/0027-5107(93)90073-o.
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 > or = (-)-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.
我们曾报道过，（+）-、（-）-和（±）-茚雌酚A和B（分别为IA和IB）在体外可抑制从猪脑中分离出的微管蛋白的聚合。在本研究中，我们用荧光抗微管蛋白抗体检测了（+）-、（-）-和（±）-IA及IB对中国仓鼠V79细胞的相对接种效率、染色体数目和细胞微管结构的影响。结果表明，（±）-IA的作用与己烯雌酚相似，（±）-IB的作用大于（±）-IA。我们还测定了旋光性IA和IB异构体的作用，发现IA和IB系列的细胞毒性活性顺序为：（-）-IA > （±）-IA > （+）-IA以及（±）-IB > 或 = （-）-IB > （+）-IB。此外，我们研究了这些化合物诱导的微管形成的细胞内紊乱情况，发现（-）-IA具有迄今为止最大的破坏作用。
