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Effects of organotin compounds on mitosis, spindle structure, toxicity and in vitro microtubule assembly.

Artikel i vetenskaplig tidskrift
Författare K G Jensen
A Onfelt
Margareta Wallin
V Lidums
O Andersen
Publicerad i Mutagenesis
Volym 6
Nummer/häfte 5
Sidor 409-16
ISSN 0267-8357
Publiceringsår 1991
Publicerad vid Zoologiska institutionen
Sidor 409-16
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Animals, Cattle, Cell Line, Cricetinae, Dose-Response Relationship, Drug, Microtubules, drug effects, Mitosis, drug effects, Mitotic Spindle Apparatus, drug effects, Organotin Compounds, toxicity, Tubulin, drug effects
Ämneskategorier Cell- och molekylärbiologi, Toxikologi

Sammanfattning

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.

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