The suitability of micronuclei as markers of relative biological effect.
The suitability of micronuclei as markers of relative biological effect.
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DOI：
10.1093/mutage/geac001
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发表时间：
2022-04-02
期刊：
影响因子：
2.7
通讯作者：
Merchant MJ
中科院分区：
文献类型：
--
作者：
Heaven CJ;Wanstall HC;Henthorn NT;Warmenhoven JW;Ingram SP;Chadwick AL;Santina E;Honeychurch J;Schmidt CK;Kirkby KJ;Kirkby NF;Burnet NG;Merchant MJ
微核（MN）的形成通常被用作辐射照射的生物剂量计，并且历史上被用作细胞中DNA损伤的量度。与剂量密切相关的MN也被建议用于指示辐射质量，区分粒子和光子照射。测量MN形成的“金标准”是Fenech的胞质分裂阻断微核（CBMN）细胞组试验，该试验使用胞质分裂阻断剂细胞松弛素B。在这里，我们提出了一个全面的分析文献调查MN诱导趋势在体外，整理193出版物，2476数据点。数据收集自使用CBMN测定来量化MN对体外电离辐射的响应的原始研究。总体而言，荟萃分析显示，个体研究的MN大多数随剂量线性增加[85%的MN/细胞（MNPC）数据集和89%的含MN百分比（PCMN）数据集的R2大于0.90]。然而，研究之间的差异很大，导致合并数据时R2较低（MNPC数据集为0.47，PCMN数据集为0.60）。颗粒类型，物种，细胞类型，细胞松弛素B浓度的建议，影响MN频率。然而，数据的变化意味着这些影响与所研究的实验参数没有很强的相关性。当比较PCMN而不是MNPC数量时，研究之间的差异较小。与CBMN方案规定的时间的偏离对MN诱导没有很大影响。然而，进一步的分析显示，严格遵循Fenech方案的研究之间的差异较小，这提供了更可靠的结果。通过限制细胞类型和物种以及仅选择遵循Fenech方案的研究，两种测量的R2均增加至0.64。因此，我们确定，由于研究之间的差异，MN目前是辐射引起的DNA损伤的预测差，并提出建议，为未来的研究评估MN，以提高数据集之间的一致性。
Micronucleus (MN) formation is routinely used as a biodosimeter for radiation exposures and has historically been used as a measure of DNA damage in cells. Strongly correlating with dose, MN are also suggested to indicate radiation quality, differentiating between particle and photon irradiation. The “gold standard” for measuring MN formation is Fenech’s cytokinesis-block micronucleus (CBMN) cytome assay, which uses the cytokinesis blocking agent cytochalasin-B. Here, we present a comprehensive analysis of the literature investigating MN induction trends in vitro, collating 193 publications, with 2476 data points. Data were collected from original studies that used the CBMN assay to quantify MN in response to ionizing radiation in vitro. Overall, the meta-analysis showed that individual studies mostly have a linear increase of MN with dose [85% of MN per cell (MNPC) datasets and 89% of percentage containing MN (PCMN) datasets had an R2 greater than 0.90]. However, there is high variation between studies, resulting in a low R2 when data are combined (0.47 for MNPC datasets and 0.60 for PCMN datasets). Particle type, species, cell type, and cytochalasin-B concentration were suggested to influence MN frequency. However, variation in the data meant that the effects could not be strongly correlated with the experimental parameters investigated. There is less variation between studies when comparing the PCMN rather than the number of MNPC. Deviation from CBMN protocol specified timings did not have a large effect on MN induction. However, further analysis showed less variation between studies following Fenech’s protocol closely, which provided more reliable results. By limiting the cell type and species as well as only selecting studies following the Fenech protocol, R2 was increased to 0.64 for both measures. We therefore determine that due to variation between studies, MN are currently a poor predictor of radiation-induced DNA damage and make recommendations for futures studies assessing MN to improve consistency between datasets.
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DOI：
10.1016/0165-1161(85)90015-9
发表时间：
1985-01-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
FENECH, M;MORLEY, AA
通讯作者：
MORLEY, AA
影响因子：
3.8
作者：
Incerti, S.;Ivanchenko, A.;Zacharatou, C.
通讯作者：
Zacharatou, C.
DOI：
10.1083/jcb.201708069
发表时间：
2017-10-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gekara NO
通讯作者：
Gekara NO
影响因子：
2.6
作者：
Höglund, E;Blomquist, E;Stenerlöw, B
通讯作者：
Stenerlöw, B
影响因子：
64.8
作者：
Andreeva, Liudmila;Hiller, Bjoern;Hopfner, Karl-Peter
通讯作者：
Hopfner, Karl-Peter