| 1. |
- Jensen, K G, et al.
(författare)
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Effects of organotin compounds on mitosis, spindle structure, toxicity and in vitro microtubule assembly.
- 1991
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Ingår i: Mutagenesis. - 0267-8357. ; 6:5, s. 409-16
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Rasmuson, Åsa, et al.
(författare)
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Somatic and germline mutagenesis assayed by the unstable zeste-white test in Drosophila melanogaster.
- 1992
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Ingår i: Mutagenesis. - 0267-8357. ; 7:3, s. 219-23
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This investigation is an attempt to compare mutation rates in germinal and somatic cells by the use of the unstable zeste-white assay in Drosophila melanogaster. In this system it is possible to use the same genetic end point to measure both somatic mutations (aberrantly pigmented spots in the eyes of adult flies) and germinal mutations (males with aberrantly pigmented eyes). We used two mutagens, formaldehyde and methylmethane sulphonate (MMS), to induce mutations and two different routes of mutagen administration, larval feeding and adult feeding, and scored mutations in somatic as well as germinal cells. Both types of tissues were susceptible to MMS mutagenesis, showing elevated frequencies of both germline mutations and eye spots. Formaldehyde, however, gave no increase in the germinal mutation rate but caused somatic mutations. These were found after larval exposure, but also among the offspring of exposed males, as formation of delayed somatic mutations. The results show that somatic cells are much more sensitive in monitoring induced mutations than germinal cells in this system. We also found that spontaneous mutation rate among germinal cells is 200 times higher than that in somatic cells, which presumably is due to the involvement of a mobile element
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