Frenzel Monika, Ricoul Michelle, Benadjaoud Mohamed Amine, Bellamy Marion, Lenain Aude, Haddy Nadia, Diallo Ibrahima, Mateus Christine, de Vathaire Florent, Sabatier Laure
a PROCyTOX (Radiation Oncology, Cytogenetics, and Toxicology Platform) , DRF Commissariat à l'Energie Atomique et aux Energies Alternatives CEA , Paris , Saclay , France.
b Radiation Epidemiology Group , INSERM U1018, Villejuif, Université Paris , Saclay , France.
Int J Radiat Biol. 2017 Oct;93(10):1040-1053. doi: 10.1080/09553002.2017.1337278. Epub 2017 Jun 26.
Cohorts allowing joint epidemiological and biological analyses are essential for radiation risk assessment. The French Hemangioma Cohort (FHC), studied within the European project EpiRadBio, is one of the rare cohorts suitable for studying the effect of low dose radiation exposure (<100 mGy at organs), with a long-term follow-up. This highly homogeneous cohort consists of healthy individuals belonging to a normal population, except for the presence of skin hemangioma (age at exposure: between 6 months and 3 years of age). Published epidemiological studies have demonstrated that the risk of developing cancer is three times higher in the exposed individuals than in the general population. Here, we present the biobanking of samples (nucleated blood cells, cytogenetic slides of T and B lymphocytes) from the FHC and a primary feasibility study of biomarker analysis focusing on mean telomere length (MTL). Telomeres act as an internal clock, regulating the lifetime of the cell by their shortening during cell division. MTL is thus a biomarker of age. Many in vitro studies have linked MTL and radiosensitivity. The FHC will make it possible to discriminate between the effects of aging and radiation on this biomarker.
The establishment of a biobank of essentially healthy individuals (369 in total), exposed 40-70 years before, during their early childhood, is a logistical challenge. Even among those who previously participated to a self-questionnaire based study, the response rate was only 30%. The first biomarker to be studied was the MTL to discriminate age effects from those of radiation exposure. MTL showed significant variation within age groups (4-11 kb) in both the exposed and non-exposed groups. MTL within the limited age window (i.e. 40-73 year) examined, showed age-dependent changes of 46 bp/year, consistent with the age-dependent decline of 41 bp/year previously reported. We observed no significant changes in MTL according to the average active bone marrow dose. However, we were able to demonstrate that exposure to radiation causes the loss of cells with, on average, shorter telomeres, by applying a model in which both the heterogeneity of the individual dose received at the bone marrow and the heterogeneity of the intercellular distribution of MTL were taken into account.
能够进行联合流行病学和生物学分析的队列对于辐射风险评估至关重要。法国血管瘤队列（FHC）是在欧洲项目EpiRadBio中进行研究的，是少数适合研究低剂量辐射暴露（器官剂量<100 mGy）影响且具有长期随访的队列之一。这个高度同质的队列由属于正常人群的健康个体组成，但存在皮肤血管瘤（暴露年龄：6个月至3岁）。已发表的流行病学研究表明，暴露个体患癌风险比普通人群高3倍。在此，我们展示了来自FHC的样本（有核血细胞、T和B淋巴细胞的细胞遗传学玻片）生物样本库以及一项聚焦于平均端粒长度（MTL）的生物标志物分析的初步可行性研究。端粒充当内部时钟，通过在细胞分裂过程中缩短来调节细胞寿命。因此，MTL是年龄的生物标志物。许多体外研究已将MTL与放射敏感性联系起来。FHC将能够区分衰老和辐射对该生物标志物的影响。
建立一个由基本健康个体（共369人）组成的生物样本库是一项后勤挑战，这些个体在幼儿期40 - 70年前曾有过暴露。即使在那些之前参与过基于自我问卷研究的人群中，回复率也仅为30%。首个被研究的生物标志物是MTL，以区分年龄效应和辐射暴露效应。在暴露组和非暴露组中，MTL在年龄组内（4 - 11 kb）均显示出显著差异。在所研究的有限年龄窗口（即40 - 73岁）内，MTL显示出每年46 bp的年龄依赖性变化，与先前报道的每年41 bp的年龄依赖性下降一致。根据平均活性骨髓剂量，我们未观察到MTL有显著变化。然而，通过应用一个同时考虑骨髓接受的个体剂量异质性和MTL细胞间分布异质性的模型，我们能够证明辐射暴露会导致平均端粒较短的细胞丢失。
