Chemically induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer.

Chemically induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer.
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哺乳动物细胞中化学诱导的非整倍性:癌症中的机制和生物学意义。

DOI:
10.1002/em.2860080112
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发表时间:
1986
期刊:
Environmental mutagenesis
影响因子:
--
通讯作者:
J. Barrett
J. Barrett
中科院分区:
--
文献类型:
--
作者:
Mitsuo Oshimura;J. Barrett

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越来越多的来自人类和动物肿瘤细胞遗传学的证据表明,非整倍体是肿瘤发生过程中的重要染色体改变。非整倍体可能与某些癌症的原发性癌变和其他肿瘤的晚期变化有关。来自体外细胞转化研究的证据支持非整倍性对正常细胞向癌前或恶性细胞的转化具有直接影响的观点。在肿瘤前或肿瘤细胞中诱导非整倍体状态可能具有以下四种生物学效应中的任何一种:基因剂量的变化、基因平衡的变化、隐性突变的表达或遗传不稳定性的变化(这可能继发性地导致肿瘤形成)。为了了解非整倍体在肿瘤发生中的作用,需要结合细胞遗传学研究进行细胞和分子研究。化学物质诱导非整倍体的可能机制有多种,包括对微管的影响、对染色体功能必需元件的损伤(即,着丝粒、复制起点和端粒),染色体凝聚或配对减少,染色体互换诱导,未解决的重组结构,染色体粘性增加,中心粒损伤,染色体排列受损,有丝分裂过程中的离子变化、核膜损伤和染色体分离的物理破坏。因此,化学诱导的非整倍性存在许多不同的靶标。由于某些化学物质诱导非整倍体的能力在哺乳动物细胞和低等真核细胞之间不同,因此研究哺乳动物细胞中非整倍体诱导的机制以及在潜在非整倍体原(诱导非整倍体的化学物质)的测定中使用哺乳动物细胞是重要的。尽管哺乳动物细胞广泛用于研究化学诱导的诱变和染色体断裂,但哺乳动物细胞的非整倍性研究是有限的。缺乏哺乳动物细胞的非整倍性遗传分析是这些研究中的一个严重限制。
A growing body of evidence from human and animal cancer cytogenetics indicates that aneuploidy is an important chromosome change in carcinogenesis. Aneuploidy may be associated with a primary event of carcinogenesis in some cancers and a later change in other tumors. Evidence from in vitro cell transformation studies supports the idea that aneuploidy has a direct effect on the conversion of a normal cell to a preneoplastic or malignant cell. Induction of an aneuploid state in a preneoplastic or neoplastic cell could have any of the following four biological effects: a change in gene dosage, a change in gene balance, expression of a recessive mutation, or a change in genetic instability (which could secondarily lead to neoplasia). To understand the role of aneuploidy in carcinogenesis, cellular and molecular studies coupled with the cytogenetic studies will be required. There are a number of possible mechanisms by which chemicals might induce aneuploidy, including effects on microtubules, damage to essential elements for chromosome function (ie, centromeres, origins of replication, and telomeres), reduction in chromosome condensation or pairing, induction of chromosome interchanges, unresolved recombination structures, increased chromosome stickiness, damage to centrioles, impairment of chromosome alignment, ionic alterations during mitosis, damage to the nuclear membrane, and a physical disruption of chromosome segregation. Therefore, a number of different targets exist for chemically induced aneuploidy. Because the ability of certain chemicals to induce aneuploidy differs between mammalian cells and lower eukaryotic cells, it is important to study the mechanisms of aneuploidy induction in mammalian cells and to use mammalian cells in assays for potential aneuploidogens (chemicals that induce aneuploidy). Despite the wide use of mammalian cells for studying chemically induced mutagenesis and chromosome breakage, aneuploidy studies with mammalian cells are limited. The lack of a genetic assay with mammalian cells for aneuploidy is a serious limitation in these studies.
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