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非洲和欧洲血统人群对基因毒性应激的反应相似吗?一项关于辐射后剂量反应的研究。

Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After Irradiation.

作者信息

Soumboundou Mamadou, Dossou Julien, Kalaga Yossef, Nkengurutse Innocent, Faye Ibrahima, Guingani Albert, Gadji Macoura, Yameogo Koudbi J, Zongo Henri, Mbaye Gora, Dem Ahmadou, Diarra Mounibé, Adjibade Rached, Djebou Catherine, Junker Steffen, Oudrhiri Noufissa, Hempel William M, Dieterlen Alain, Jeandidier Eric, Carde Patrice, El Maalouf Elie, Colicchio Bruno, Bennaceur-Griscelli Annelise, Fenech Michael, Voisin Philippe, Rodriguez-Lafrasse Claire, M'Kacher Radhia

机构信息

Laboratoire Biophysique UFR-Santé, Dakar, Senegal.

Département du Génie d'Imagerie Médicale et Radiobiologie, Cotonou, Benin.

出版信息

Front Genet. 2021 Nov 11;12:657999. doi: 10.3389/fgene.2021.657999. eCollection 2021.

DOI:10.3389/fgene.2021.657999
PMID:34868192
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8632650/
Abstract

Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry. Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0-4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations. No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes ( = 8.65 10), centric rings ( = 4.0310), and resulting double-strand-breaks (DSB) ( = 1.32 10) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa. This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.

摘要

暴露于辐射等遗传毒性应激是一个影响大量人群的重要公共卫生问题。分析此类暴露的细胞遗传学效应的必要性与估计相关风险的需求有关。细胞遗传学生物剂量测定基于吸收剂量与计分染色体畸变频率之间的关系。混杂因素对辐射反应的影响是一个热门话题。种族的作用尚不清楚。在这里,我们比较了来自非洲和欧洲血统健康供体的循环淋巴细胞照射后获得的剂量反应曲线。使用X-RAD320辐照器,以0.1 Gy/分钟的剂量率,将来自生活在非洲的6名非洲人、生活在欧洲的5名非洲人和生活在欧洲的5名高加索人的血样暴露于不同剂量(0-4 Gy)的X射线下。纳入了一个由生活在三个非洲国家的14名健康非洲人组成的经过验证的队列,并使用相同方案对血样进行照射。血淋巴细胞培养48小时,并通过端粒和着丝粒染色在第一次有丝分裂期间计分染色体畸变。确定双着丝粒染色体的分布,并使用Kruskal-Wallis检验比较两个人群的剂量反应曲线。在非洲供体中未检测到自发双着丝粒染色体,因此相对于欧洲人群确定了非常低的不稳定染色体畸变背景。非洲本地供体和欧洲供体之间的剂量反应曲线存在显著差异。在4 Gy时,非洲供体的双着丝粒染色体(= 8.65×10)、着丝粒环(= 4.03×10)和由此产生的双链断裂(DSB)(= 1.32×10)频率明显低于欧洲供体。此外,生活在欧洲的非洲供体与生活在非洲的非洲人之间存在显著差异。这是第一项证明种族和环境因素可能通过表观遗传影响辐射反应的重要作用的研究。有必要建立原产国特定的剂量反应曲线以进行精确和充分的生物剂量测定。这项工作为基于遗传毒性剂(如辐射)的治疗比较开辟了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/976f797578f9/fgene-12-657999-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/bf472744d29b/fgene-12-657999-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/b0588d076f2d/fgene-12-657999-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/840a49a1d2d9/fgene-12-657999-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/976f797578f9/fgene-12-657999-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/bf472744d29b/fgene-12-657999-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/b0588d076f2d/fgene-12-657999-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/840a49a1d2d9/fgene-12-657999-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23ec/8632650/976f797578f9/fgene-12-657999-g004.jpg

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