Research projects
Exposure of the population to radiation can be natural, medical or professionally related. Scientific knowledge contributing to a better understanding of the harmful effects of radiation contributes to more effective protection of the public.
Following irradiation, most DNA damage is repaired in a few hours. Mutations that persist are usually recessive and remain silent until the occurrence of a mutation on the second allele that may result from telomere dysfunction related to cellular aging or by damage to the telomere itself. Such events are very unlikely for low doses of radiation.
The main research themes of the LRO focus on the relationship between cells with radio-induced damage, the fate of these cells during cell development, genetic instability and tumor progression.
Transmission of radio-induced damage and its relation to cellular aging.
Primary cancers are of multifactorial origin. Approximately 15% of patients who undergo radiotherapy develop radiation-induced secondary cancers 10 to 20 years later. The results of early studies have shown that the presence of short telomeres contributes to genetic instability in the progeny of irradiated cells. Furthermore, telomere dysfunction is implicated in radio-induced genomic instability and cellular radiosensitivity. Our research on human cells focuses on the mechanisms involved in the process of instability following telomere loss. We, therefore, study the transmission of radiation-induced chromosomal damage and telomere alterations in the progeny of irradiated cells. In order to determine the impact of the state of telomeres on genomic stability and individual susceptibility to develop cancer long after low dose irradiation, we are performing a study on a French cohort of hemangioma patients exposed or not to radiation in collaboration with the laboratory of Florent deVathaire (INSERM U1018 / IGR). In this study, we are analyzing the intra- and intercellular heterogeneity of telomere length. We use nucleated blood cells, in particular B and T lymphocytes, 40-60 years after treatment to assess chromosomal instability related to telomere length. This molecular epidemiological approach was initiated in 2011 as part of the European project EPIRADBIO (2011-2015). As part of this project we have managed all administrative and regulatory issues (CCTIRS agreement, CNIL) to create the biobank and perform an initial study of 400 exposed /non-exposed donors who have not developed cancer prior to the day their inclusion. This work represents the first retrospective molecular epidemiology study on "normal" ie non-cancer patients who received low doses of radiation (<100 mGy) thus addressing a dose range for which there is no available data for humans (the limit of data from existing epidemiological studies show no effect below 100 mGy, requiring extrapolation, which is by default linear and no threshold is estimated.
Biodosimetry and technological innovation
In a radiological or nuclear accident, triage of the irradiated population should be performed in the days following exposure to optimize the management of individuals and adapt their treatment as a function of the radiation dose. The reference dosimetry technique is biological dosimetry by the quantification of chromosomal aberrations (dicentrics and rings) after uniform Giemsa staining. This technique involves a time incompressible period of cell culture (2 days) and analysis by cytogenetics experts. We have developed a technique for quantifying chromosome aberrations based on the staining of telomeres and centromeres (PNA-FISH) that we have made robust and reproducible. With this technique, the quantification of anomalies can be automated to achieve the same efficiency as for manual counting MKacher et al, 2014. In order to increase the speed of providing the dose estimate, we have applied the telomere-centromere labeling technique to prematurely condensed chromosomes (PCC). This approach allows the removal of the cell culture step (48h). The cells (interphase nuclei) are fused with mitotic Hamster cells which induce premature chromosome condensation. This work is performed in collaboration with the European laboratory with the greatest expertise in this technique (Gabriel Pantelias Demokritos, Athens). We have established a dose response curve and the automated counting of anomalies, Mkacher et al, 2015. New techniques for the quantification of genomic damage are being validated. Inter-comparison exercises are being carried out within the European project RENEB.