Jensen K G, Onfelt A, Wallin M, Lidums V, Andersen O
Department of Environmental Medicine, Odense University, Denmark.
Mutagenesis. 1991 Sep;6(5):409-16. doi: 10.1093/mutage/6.5.409.
Di- and tri-methyl, -butyl and phenyl tin, all as chlorides were tested for toxicity and spindle disturbances in V79 Chinese hamster cells and for effects on in vitro assembly of bovine brain tubulin. The V79 cells were treated for 30 min and in general, loss of a stainable spindle could be demonstrated at slightly higher concentrations than c-mitosis. Both these effects were observed at low, non-toxic concentrations. The c-mitotic activity of the compounds was found to increase with increasing lipophilicity and it was best described by a regression on both lipophilicity (partition coefficient octanol/water) and loss of spindle stain. All compounds showed a concentration dependent inhibition of microtubule assembly and all but diphenyltin induced disassembly of preassembled microtubules. An effect on the rate of polymerization was suggested for tributyl- and triphenyltin. The results further indicate that the inhibition of microtubule assembly is through direct interaction with tubulin but does not involve the sulfhydryls of the protein. Thus, the organotins seem to act through two different cooperative mechanisms, inhibition of microtubule assembly and interaction with hydrophobic sites. The latter mechanism might involve Cl-/OH- exchange across cellular membranes. Previous studies have demonstrated chromosomal supercontraction and aneuploidy in human lymphocytes exposed to low concentrations of organotin in vitro and it is suggested that exposure to these compounds may increase the risk of aneuploidy in humans.
二甲基、三甲基、丁基和苯基锡的氯化物均被测试了对V79中国仓鼠细胞的毒性和纺锤体干扰作用，以及对牛脑微管蛋白体外组装的影响。V79细胞处理30分钟，一般来说，在略高于c-有丝分裂的浓度下就能证明可染色纺锤体的丧失。在低的、无毒的浓度下就观察到了这两种效应。发现这些化合物的c-有丝分裂活性随着亲脂性的增加而增加，用亲脂性（正辛醇/水分配系数）和纺锤体染色丧失的回归来描述最为合适。所有化合物都表现出浓度依赖性的微管组装抑制作用，除二苯基锡外，所有化合物都能诱导预先组装好的微管解聚。三丁基锡和三苯基锡对聚合速率有影响。结果进一步表明，微管组装的抑制是通过与微管蛋白的直接相互作用，但不涉及蛋白质的巯基。因此，有机锡似乎通过两种不同的协同机制起作用，即抑制微管组装和与疏水位点相互作用。后一种机制可能涉及跨细胞膜的Cl-/OH-交换。先前的研究表明，体外暴露于低浓度有机锡的人淋巴细胞会出现染色体超收缩和非整倍体，有人认为接触这些化合物可能会增加人类非整倍体的风险。
