関: demecolcine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/14 14:37:32」(JST)

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Used in cytogenetics, colcemid, also known as demecolcine, is related to colchicine but it is less toxic. It depolymerises microtubules and limits microtubule formation (inactivates spindle fibre formation), thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.

Mechanism of Action

Colcemid is a microtubule-depolymerizing drug like vinblastine. It acts by two distinct mechanisms. At very low concentration it binds to microtubule plus end to suppress microtubule dynamics.^[1] Recent study has found at higher concentration colcemid can promote microtubule detachment from microtubule organizing center. Detached microtubules with unprotected minus ends depolymerize with time. Cytotoxicity of the cells seems to correlate better with microtubule detachment.^[2] Lower concentrations affect microtubule dynamics and cell migration.^[2]

Uses

Colcemid is used primarily for scientific research in cells. It is used in a variety of ways, however, until recently, was used mostly for the study of mitosis in cells. For example, microtubules are necessary for the splitting of cells. More importantly, the movement of chromosomes during the M phase. Colcemid inhibition of microtubules causes aneuploidy in mitotic cells where the microtubules fall apart or are suppressed before they can complete their function of pulling chromosomes into the daughter cell, also known as nondisjunction of chromosomes.^[3] Colcemid, depending on dosage, has also been found to cause DNA fragmentation of chromosomes in micronuclei when nondisjunction occurs.^[4]

References

^ Jordan, Mary Ann; Wilson, Leslie (2004). "Microtubules as a target for anticancer drugs". Nature reviews. Cancer 4 (4): 253–65. doi:10.1038/nrc1317. PMID 15057285.
^ ^a ^b Yang, Hailing; Ganguly, Anutosh; Cabral, Fernando (2010). "Inhibition of Cell Migration and Cell Division Correlates with Distinct Effects of Microtubule Inhibiting Drugs". The Journal of Biological Chemistry 285 (42): 32242–50. doi:10.1074/jbc.M110.160820. PMC 2952225. PMID 20696757.
^ Hashimoto, Kiyohiro; Todo, Takeshi (2013-07-01). "Mitotic slippage underlies the relationship between p53 dysfunction and the induction of large micronuclei by colcemid". Mutagenesis 28 (4): 457–464. doi:10.1093/mutage/get021. ISSN 0267-8357. PMID 23702691.
^ Yamamoto, Mika; Wakata, Akihiro; Aoki, Yoshinobu; Miyamae, Yoichi; Kodama, Seiji (2014-04-01). "Chromosome loss caused by DNA fragmentation induced in main nuclei and micronuclei of human lymphoblastoid cells treated with colcemid". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 762: 10–16. doi:10.1016/j.mrfmmm.2014.02.002.

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1. 慢性骨髄性白血病における造血細胞移植 hematopoietic cell transplantation in chronic myeloid leukemia

English Journal

Evaluation of drugs and stationary growth on the cell cycle of Giardia intestinalis.

Reaume C, Moore B, Hernández P, Ruzzini A, Chlebus M, Wasserman M, Yee J.SourceDepartment of Biology, Biochemistry Program, Trent University, Peterborough, Ontario K9J 7B8, Canada.
Molecular and biochemical parasitology.Mol Biochem Parasitol.2012 Dec 5;187(1):72-76. doi: 10.1016/j.molbiopara.2012.11.005. [Epub ahead of print]
We examined the effect of aphidicolin, colchicine, demecolcine, fluorouracil, hydroxyurea, and nocodazole, as well as nutrient deprivation on the Giardia intestinalis cell cycle. Aphidicolin was the only drug that was able to block the cell cycle at a specific stage (G1/S), and permit cells to resum
PMID 23220085

Replication of somatic micronuclei in bovine enucleated oocytes.

Canel N, Bevacqua R, Hiriart MI, Salamone D.AbstractABSTRACT: BACKGROUND: Microcell-mediated chromosome transfer (MMCT) was developed to introduce a low number of chromosomes into a host cell. We have designed a novel technique combining part of MMCT with somatic cell nuclear transfer, which consists of injecting a somatic micronucleus into an enucleated oocyte, and inducing its cellular machinery to replicate such micronucleus. It would allow the isolation and manipulation of a single or a low number of somatic chromosomes.
Cell division.Cell Div.2012 Nov 22;7(1):23. [Epub ahead of print]
ABSTRACT: BACKGROUND: Microcell-mediated chromosome transfer (MMCT) was developed to introduce a low number of chromosomes into a host cell. We have designed a novel technique combining part of MMCT with somatic cell nuclear transfer, which consists of injecting a somatic micronucleus into an enucle
PMID 23173571

Effects of spindle poisons in peripheral human lymphocytes by the in vitro cytokinesis-block micronucleus assay.

Guccini S, Lombardi S, Pisani A, Piaggi S, Scarpato R.SourceDipartimento di Biologia (Unità di Genetica, Mutagenesi e Epidemiologia Ambientale), University of Pisa, via Derna 1, 56100 Pisa, Italy.
Mutagenesis.Mutagenesis.2012 Nov;27(6):749-58. doi: 10.1093/mutage/ges044. Epub 2012 Sep 5.
The search for micronuclei (MN) in binucleated cells is not always the best choice to recognize microtubule-perturbing agents, as they give rise to (micronucleated) mononucleated cells, mainly via mitotic slippage. We therefore treated peripheral lymphocytes with vincristine (VCR), nocodazole (NOC)
PMID 22952150

Japanese Journal

Recurrent micronucleation through cell cycle progression in the presence of microtubule inhibitors

Nakayama Yuji,Uno Narumi,Uno Katsuhiro,Mizoguchi Yamato,Komoto Shinya,Kazuki Yasuhiro,Nanba Eiji,Inoue Toshiaki,Oshimura Mitsuo
Cell Structure and Function advpub(0), 2015
… Among these cells, limited numbers of rodent cells are known to undergo multinucleation to generate multiple small independent nuclei, or micronuclei by prolonged colcemid treatment. … To better define this process, we used long-term live cell imaging to observe micronucleation induced in mouse A9 cells by treating with the microtubule inhibitor colcemid. …
NAID 130004885870

Recurrent Micronucleation through Cell Cycle Progression in the Presence of Microtubule Inhibitors

Nakayama Yuji,Uno Narumi,Uno Katsuhiro,Mizoguchi Yamato,Komoto Shinya,Kazuki Yasuhiro,Nanba Eiji,Inoue Toshiaki,Oshimura Mitsuo
Cell Structure and Function 40(1), 51-59, 2015
… Among these cells, limited numbers of rodent cells are known to undergo multinucleation to generate multiple small independent nuclei, or micronuclei by prolonged colcemid treatment. … To better define this process, we used long-term live cell imaging to observe micronucleation induced in mouse A9 cells by treating with the microtubule inhibitor colcemid. …
NAID 130004885868

The Effect of Nickel and Zinc Addition to Rabbit Feed in Conjunction with the Risk of Chromosomal Aneuploidy

Curlej Jozef,Massanyi Peter,Chrenek Peter
CYTOLOGIA 77(2), 181-185, 2012
… Chromosome preparations were obtained from blood lymphocytes after metaphase arrest using colcemid solution. …
NAID 130004448179