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

Frontiers in Genetics

Elie El Maalouf¹  Bruno Colicchio²  Philippe Voisin³  Claire Rodriguez-Lafrasse⁴  Radhia M’Kacher⁵  Michael Fenech⁶  William M. Hempel⁶  Alain Dieterlen⁷  Ibrahima Faye⁷  Annelise Bennaceur-Griscelli⁷  Macoura Gadji⁸  Gora Mbaye⁸  Henri Zongo⁸  Yossef Kalaga⁸  Eric Jeandidier⁹  Albert Guingani⁹  Catherine Djebou^1,10  Julien Dossou^1,10  Steffen Junker^1,10  Patrice Carde^1,11  Noufissa Oudrhiri^1,12  Ahmadou Dem^1,13  Rached Adjibade^1,13  Mamadou Soumboundou^1,13  Innocent Nkengurutse^1,14  Mounibé Diarra^1,15  Koudbi J. Yameogo^1,15 

[1] 0Service de Génétique Groupe Hospitalier de la Région de Mulhouse et Sud Alsace, Mulhouse, France;1Department of Hematology, Gustave Roussy Cancer Campus, Villejuif, France;2School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia;3Genome Health Foundation, North Brighton, SA, Australia;4Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;APHP-Service d’Hématologie – Oncohématologie Moléculaire et Cytogénétique Hôpital Paul Brousse Université Paris Saclay/Inserm UMR 935, Villejuif, France;;Cell Environment, DNA Damage R&Centre Hospitalier Yalgado Radioprotection-Radiobiologie, Ouagadougou, Burkina Faso;D, Paris, France;Département du Génie d’Imagerie Médicale et Radiobiologie, Cotonou, Benin;IRIMAS, Institut de Recherche en Informatique, Mathématiques, Automatique et Signal, Université de Haute-Alsace, Mulhouse, France;Institute of Biomedicine, University of Aarhus, Aarhus, Denmark;Laboratoire Biophysique UFR-Santé, Dakar, Senegal;Laboratoire de Radiobiologie, Bujumbura, Burundi;Service Hématologie UCAD, Dakar, Senegal;

关键词: African donors;    European donors;    irradiation;    dicentric chromosome;    telomeres;    centromeres;   

DOI  :  10.3389/fgene.2021.657999

来源: DOAJ

【 摘 要 】

Background: 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.Materials and Methods: 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.Results: 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 (p = 8.65 10–17), centric rings (p = 4.0310–14), and resulting double-strand-breaks (DSB) (p = 1.32 10–18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa.Conclusion: 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.

【 授权许可】

Unknown