Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond.

Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond.
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DOI:
10.3389/fgene.2013.00131
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发表时间:
2013
影响因子:
3.7
通讯作者:
Kovalchuk O
Kovalchuk O
中科院分区:
生物学3区
文献类型:
--
作者:
Luzhna L;Kathiria P;Kovalchuk O

文献摘要

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微核 (MN) 是核外体,包含细胞分裂后未并入细胞核的受损染色体片段和/或整个染色体。细胞修复机制的缺陷以及 DNA 损伤和染色体畸变的积累可以诱发 MN。多种基因毒性剂可能诱导 MN 形成,导致细胞死亡、基因组不稳定或癌症发展。在这篇综述中,描述了对细胞分裂和细胞周期的各种致畸和非整生效应后 MN 形成的遗传和表观遗传机制。准确反映了文献中积累的有关各种基因毒素细胞毒性的知识,并讨论了由于单基因多态性而导致的个体对 MN 形成的敏感性。还评估了快速 MN 评分对于胞质分裂阻断微核测定的重要性。
Micronuclei (MN) are extra-nuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division. MN can be induced by defects in the cell repair machinery and accumulation of DNA damages and chromosomal aberrations. A variety of genotoxic agents may induce MN formation leading to cell death, genomic instability, or cancer development. In this review, the genetic and epigenetic mechanisms of MN formation after various clastogenic and aneugenic effects on cell division and cell cycle are described. The knowledge accumulated in literature on cytotoxicity of various genotoxins is precisely reflected and individual sensitivity to MN formation due to single gene polymorphisms is discussed. The importance of rapid MN scoring with respect to the cytokinesis-block micronucleus assay is also evaluated.