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Titolo:
Spindle poisons induce allelic loss in mouse lymphoma cells through mitotic non-disjunction
Autore:
Honma, M; Momose, M; Sakamoto, H; Sofuni, T; Hayashi, M;
Indirizzi:
Natl Inst Hyg Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 1588501, Japan Natl Inst Hyg Sci Tokyo Japan 1588501 Setagaya Ku, Tokyo 1588501, Japan Olympus Opt Co Ltd, Chromosome Res Ctr, Tokyo, Japan Olympus Opt Co Ltd Tokyo Japan Co Ltd, Chromosome Res Ctr, Tokyo, Japan
Titolo Testata:
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
fascicolo: 1-2, volume: 493, anno: 2001,
pagine: 101 - 114
SICI:
1383-5718(20010627)493:1-2<101:SPIALI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHEMICALLY-INDUCED ANEUPLOIDY; MICROTUBULE ASSEMBLY INVITRO; HUMAN LYMPHOBLASTOID-CELLS; ANTI-CANCER DRUGS; WILD-TYPE P53; TK-/ MUTANTS; CHINESE-HAMSTER; MAMMALIAN-CELLS; TRIFLUOROTHYMIDINE-RESISTANT; CYTOGENETIC ANALYSIS;
Keywords:
mouse lymphoma assay (MLA); colchicine; vinblastine; loss of heterozygosity (LOH); mitotic non-disjunction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Honma, M Natl Inst Hyg Sci, Div Genet & Mutagenesis, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan Natl Inst Hyg Sci 1-18-1 Kamiyoga Tokyo Japan 1588501 501, Japan
Citazione:
M. Honma et al., "Spindle poisons induce allelic loss in mouse lymphoma cells through mitotic non-disjunction", MUT RES-GTE, 493(1-2), 2001, pp. 101-114

Abstract

Aneuploidy is an important contributor to reproductive failure and tumor development. It arises spontaneously or as a result of exposure to aneugenicagents through non-disjunction. Two spindle poisons, colchicine (COL) and vinblastine (VBL) are mutagenic in the mouse lymphoma assay (MLA), a gene mutation assay that targets the heterozygous thymidine kinase (tk) gene on chromosome II in mouse lymphoma L5178Y tk+/- 3.7.2c cells. To investigate the mechanisms of spindle poison mutagenesis, we analyzed the COL- and VBL-induced TK mutants at the molecular and cytogenetic level. Loss of heterozygosity (LOH) analysis employing a microsatellite region within the tk locus revealed that almost all mutants had lost the functional tk allele. To determine the extent of the LOH, we further examined LOH mutants for heterozygosity at nine microsatellite loci spanning the entire chromosome Il. Interestingly, every microsatellite marker showed LOH in all COL- and VBL-induced LOH mutants, suggesting that these mutants were generated by loss of the whole chromosome 11 through mitotic non-disjunction. Chromosome painting analysis supported this hypothesis; there were no mutants showing structural changes such as deletions or translocations involving chromosome Ii. In contrast, spontaneous TK mutants followed from point mutations, deletions and recombinational events as well as whole chromosome loss. Our present study indicates that spindle poisons induce mutations through mitotic non-disjunction without structural DNA changes and supports a possible mechanism in whicha recessive mutation mediated by aneuploidy may develop tumors. (C) 2001 Elsevier Science B.V. All rights reserved.

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Documento generato il 05/04/20 alle ore 21:47:12