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博来霉素对人淋巴细胞中完全和不完全染色体畸变的诱导作用。

Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes.

作者信息

Benkhaled L, Xunclà M, Caballín M R, Barrios L, Barquinero J F

机构信息

Universitat Autònoma de Barcelona, Unitat d'Antropologia Biológica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193, Bellaterra, Spain.

出版信息

Mutat Res. 2008 Jan 1;637(1-2):134-41. doi: 10.1016/j.mrfmmm.2007.07.013. Epub 2007 Aug 3.

Abstract

Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation (~0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.

摘要

博来霉素(BLM)是一种致断裂化合物,由于其诱导的双着丝粒在细胞分布中存在过度离散现象,已被拿来与高传能线密度辐射的效应作比较。最近有描述称,在成纤维细胞衍生的细胞系中,BLM诱导不完全染色体元件的效率比任何类型的电离辐射都更高。本研究的目的是评估BLM在人淋巴细胞中诱导双着丝粒和不完全染色体元件的情况。外周血样本用不同浓度的BLM进行了处理。应用了两种细胞遗传学技术,即荧光加吉姆萨(FPG)以及使用全着丝粒和全端粒探针的荧光原位杂交(FISH)。观察到的双着丝粒当量频率随BLM浓度呈线性增加,并且对于所有BLM浓度,双着丝粒当量的分布都是过度离散的。在FISH研究中,总不完全元件与多着丝粒之间的比率为0.27。双着丝粒细胞分布中的过度离散以及双着丝粒对BLM浓度的线性依赖性可与高传能线密度辐射的效应相比较,相反,不完全元件与多着丝粒的比率与低传能线密度辐射诱导的比率相似(约为0.40)。与总无着丝粒片段相比,间质缺失的比例升高,高于任何类型的电离辐射,这可能是BLM致断裂效应的一个特征性标志。

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