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The aim of this review paper is to clarify the radio-induced breast cancer (BC) risk in BRCA mutation carriers with a combined epidemiological and radiobiological comprehensive approach. A systematic literature search on PubMed (MEDLINE) and EMBASE was performed for articles published from January 1st, 2000 to June 15th, 2017 using dedicated key words as subject headings (MeSH) in three domains of research and evaluation: risk modeling, cohort-studies and ex-vivo radiation biology with epithelial non-tumoral human breast cells. Only eleven articles that meet the selection criteria could be retrieved. These articles are analyzed and discussed. This review, which includes all types of radiological breast exposures, shows an association between BC risk and low cumulative X-ray doses before age 30. There is no consistent data in this literature regarding the risk of BC from radiological exposure after age 30. Biological data point out strong indicators of radiation-induced genomic instability linked with carcinogenesis pathways. We conclude that the risk of radio-induced BC in BRCA mutation carriers depends on age at exposure and that repeated X-ray breast exposures such as mammography should be used very cautiously in these mutated patients.

Bronchiolitis obliterans with organizing pneumonia is an inflammatory reaction that can occur as a consequence of various pulmonary affections. Radiotherapy is not the sole and systematic cause of bronchiolitis obliterans with organizing pneumonia. Radiation-induced should not be confused with post-radiation, dose-dependent, inflammatory pulmonary fibrosis, which is non-immunological and located within the irradiation field. The role of immunity, local inflammation and individual radiosensitivity in bronchiolitis obliterans with organizing pneumonia is not well defined. Bronchiolitis obliterans with organizing pneumonia represents 1% of irradiated patients with breast cancer. It results in fever (flu-like symptoms), a rather dry cough and dyspnea. In the post-radiation context, bronchiolitis obliterans with organizing pneumonia may be diagnosed several months and up to a year after breast irradiation. The treatment consists of prolonged steroids or immunosuppressants, which do not prevent chronicity in 15% of patients and death in up to 5% of cases, the remaining 80% of patients healing without sequelae.

Étienne Destot is a French physician from Burgundy who benefited, during his studies in Lyon, from the quality of teaching of the best specialists of the time: Augagneur for hygiene, Testut for anatomy, Ollier for surgery, Lépine for the medical applications of electricity and the Lumière brothers for the technological development. During its experiments, he met Despeignes, the first radiation oncologist, Regaud pioneer of radiobiology and Bouchacourt who pointed out individual radiosensitivity. Less than two months after the X-rays discovery by Roentgen, he produced one of the first French radiographic views that were at the origin of our current knowledge in bone and cartilage anatomy and traumatology. He funded the first department of radiology in France in a former library of the major hospital of Lyon, where he made a number of original advances. It appears obvious that, while Antoine Beclère was the great organizer of the French radiology, Destot was its pathfinder. Destot was at the origin of several technological advances that gave stereoscopy, internal organs imaging and quantification of the heart-thorax ratio. By contrast, he was not convinced of the therapeutic properties of X-rays even if he contributed to the technological development of X-ray tubes. Victim of radiations, exhausted, Destot died on December 1918, by helping the Great War victims. His name is written in a war tribute monument in Arc-et-Senans (Burgundy).

Resume Chaque developpement technologique de la radiotherapie est un exemple d’interaction entre medecins et physiciens. Cela a ete le cas avec les premiers generateurs de rayons X, les betatrons et les premiers accelerateurs de particules. C’est le cas aujourd’hui pour la radiotherapie Cyberknife®, celle avec modulation d’intensite et celle par protons. Ce sera bientot le cas pour les ions lourds. Cependant, dans une tendance generale d’utilisation d’energies de plus en plus elevees, abandonnant les appareils de 250 kV au profit d’accelerateurs delivrant des photons d’une vingtaine de MeV qui permettent d’atteindre les tumeurs les plus profondes, comment considerer les applications therapeutiques recentes mettant en jeu le rayonnement synchrotron qui ne fournit « que » des rayons X de 10 a 100 keV ? Depuis les premieres approches de photoactivation nees aux Etats-Unis dans les annees 1970 jusqu’aux derniers tests precliniques effectues au synchrotron europeen de Grenoble, les aspects radiobiologiques de la chimioradiotherapie par rayonnement synchrotron seront decrits et analyses a travers une vision transversale faisant cohabiter les aspects physicochimiques fondamentaux, les mecanismes biomoleculaires et cellulaires et les resultats des tests precliniques afin d’en tirer un bilan scientifique et d’eventuelles perspectives de transfert.

The linear-quadratic (LQ) model is the only mathematical formula linking cellular survival and radiation dose that is sufficiently consensual to help radiation oncologists and radiobiologists in describing the radiation-induced events. However, this formula proposed in the 1970s and α and β parameters on which it is based remained without relevant biological meaning. From a collection of cutaneous fibroblasts with different radiosensitivity, built over 12 years by more than 50 French radiation oncologists, we recently pointed out that the ATM protein, major actor of the radiation response, diffuses from the cytoplasm to the nucleus after irradiation. The evidence of this nuclear shuttling of ATM allowed us to provide a biological interpretation of the LQ model in its mathematical features, validated by a hundred of radiosensitive cases. A mechanistic explanation of the radiosensitivity of syndromes caused by the mutation of cytoplasmic proteins and of the hypersensitivity to low-dose phenomenon has been proposed, as well. In this review, we present our resolution of the LQ model in the most didactic way.

Type I neurofibromatosis (NF) is the most common autosomal dominant disease. It concerns one in 3000 births, the penetrance is close to 100% and 50% of new cases are de novo mutations (17q11.2 chromosome 17 location). Cranio-maxillofacial region is concerned in 10% of the cases, in different forms: molluscum neurofibroma, plexiform neurofibroma, cranio-orbital neurofibroma, parotido-jugal neurofibroma, cervical neurofibroma. These lesions have different prognosis depending on the craniofacial localization: ocular functional risk, upper airway compressive risk, nerve compression risk, aesthetic and social impact. The maxillofacial surgeon in charge of patients with type I NF should follow the patient from the diagnosis and organize the different surgical times in order to take care about the different issues: vital, functional and aesthetic. We describe the treatment of facial localizations of type 1 NF as it is done at the University Hospital of Lyon and at the Rhône-Alpes-Auvergne neurofibromatosis reference center.

The dose fractionation effect is a recurrent question of radiation biology research that remains unsolved since no model predicts the clinical effect only with the cumulated dose and the radiobiology of irradiated tissues. Such an important question is differentially answered in radioprotection, radiotherapy, radiology or epidemiology. A better understanding of the molecular response to radiation makes possible today a novel approach to identify the parameters that condition the fractionation effect. Particularly, the time between doses appears to be a key factor since it will permit, or not, the repair of certain radiation-induced DNA damages whose repair rates are of the order of seconds, minutes or hours: the fractionation effect will therefore vary according to the functionality of the different repair pathways, whatever for tumor or normal tissues.

To overcome the underestimation of the small residual damage when measuring DNA double-strand breaks (DSB) as fraction of activity released (FAR) by pulsed-field gel electrophoresis.The techniques used to assess DNA damage (e.g. pulsed-field gel electrophoresis, neutral elution, comet assay) do not directly measure the number of DSB. The Blöcher model can be used to express data as DSB after irradiation at 4 degrees C by calculating the distribution of all radiation-induced DNA fragments as a function of their size. We have used this model to measure the residual DSB (irradiation at 4 degrees C followed by incubation at 37 degrees C) in untransformed human fibroblasts.The DSB induction rate after irradiation at 4 degrees C was 39.1+/-2.0 Gy(-1). The DSB repair rate obtained after doses of 10 to 80 Gy followed by repair times of 0 to 24 h was expressed as unrepaired DSB calculated from the Blöcher formula. All the damage appeared to be repaired at 24h when the data were expressed as FAR, whereas 15% of DSB remained unrepaired. The DSB repair rate and the chromosome break repair rate assessed by premature condensation chromosome (PCC) techniques were similar.The expression of repair data in terms of FAR dramatically underestimates the amount of unrepaired DNA damage. The Blöcher model that takes into account the size distribution of radiation-induced DNA fragments should therefore be used to avoid this bias. Applied to a normal human fibroblast cell line, this model shows that DSB repair is never complete.

Les cassures double-brin (CDB) de l'ADN constituent l'evenement-cle susceptible d'expliquer l'effet letal des radiations ionisantes. Une revue generale de la litterature montre que, a l'exception d'un groupe minoritaire de tumeurs humaines, c'est surtout une deficience de reparation plutot que l'incidence des degâts qui est associee a la mort des cellules de mammiferes irradiees. Toutefois, les arguments en faveur d'un lien entre radiosensibilite et CDB sont generalement indirects. A partir de 23 lignees fibroblastiques humaines (5 temoins et 18 hypersensibles), nous decrivons une relation quantifiee entre la radiosensibilite intrinseque et les cassures residuelles de l'ADN et des chromosomes. La mort d'un fibroblaste humain irradie est associee a 6,6 CDB et 1,3 cassure chomosomique non reparees.

To propose a novel interpretation of DNA double-strand break (dsb) repair based on the distribution of energy micro-deposition.Double-strand break repair curves were studied either after irradiation at 4 degrees C or at 37 degrees C (low dose rate). Two human fibroblast cell lines were used: a control line, HF19, and an ataxia telangiectasia repair-deficient line, AT5BI. Irradiations were made with gamma-rays or alpha-particles (241Am). Repair data were fitted by the variable repair half-time (VRHT) model. Assuming that each dsb has its own inherent repair half-time (IRHT) and that the VRHT is the average of the IRHT at any time during repair, the distribution of the IRHT was calculated.At the end of the irradiation, the distribution was a continuous asymmetric curve with a maximum of dsb having a short IRHT. After 1 h of repair, the curve became bell-shaped. There is a striking similarity between the distribution of dsb repair half-times and that of energy micro-deposition described by Goodhead et al. (1993).This similarity suggests a possible causal relationship between the energy density deposition and the repair rate or the probability of dsb repair.

A large number of reports suggest that DNA double-strand breaks (DSB) play a major role in the radiation-induced killing of mammalian cells. However, the arguments supporting the relationship between DSB and radiosensitivity are generally indirect. Furthermore, care must be taken to allow for the possible impact of the techniques and of the experimental protocols on the relationship between DSB and cell death. The recent data on DSB induction, repair and misrepair in human cell lines and their correlation with intrinsic radiosensitivity are reviewed.

At the beginning of the 21st century, radiation biology is at a major turning point in its history. It must meet the expectations of the radiation oncologists, radiologists and the general public, but its purpose remains the same: to understand the molecular, cellular and tissue levels of lethal and carcinogenic effects of ionizing radiation in order to better protect healthy tissues and to develop treatments more effective against tumours. Four major aspects of radiobiology that marked this decade will be discussed: technological developments, the importance of signalling and repair of radiation-induced deoxyribonucleic acid (DNA) damage, the impact of individual factor in the response to radiation and the contribution of radiobiology to better choose innovative therapies such as protontherapy or stereotactic body radiation therapy (SBRT). A translational radiobiology should emerge with the help of radiotherapists and radiation physicists and by facilitating access to the new radio and/or chemotherapy modalities.

Each technological development of radiotherapy is an example of interaction between physicians and physicists. In the past, it was the case for the first X-rays generators, betatrons and particle accelerators. To date, this is the case for Cyberknives and intensity modulation radiotherapy. In the future, this will be the case for proton- and hadron-therapy. However, in a general tendency of favouring higher radiation energies, leaving the 250kV orthovoltage irradiators and preferring accelerators delivering some tens MeV to reach the deepest tumours, how to consider the anti-cancer applications of synchrotron radiation that provides X-rays in the 10-100keV "only"? Since the first approaches developed in the USA in seventies until the last preclinical trials performed at the European Synchrotron Radiation Facility of Grenoble, the radiobiological features of the chemoradiotherapy involving synchrotron radiation will be described and analysed throughout a transversal view considering physicochemical bases, biomolecular and cellular mechanisms and results from the preclinical trials in order to provide a general outcome and some eventual transfer perspectives.

International audience; Among the large spectrum of DNA damage induced by radiation, DNA double-strand breaks (DSBs) are considered, to date, as the key-lesions responsible for the cell killing. However, although it was always intuitive to radiobiologists, such a conclusion has only been reached after technical developments and conceptual advances and remains consensual rather than demonstrated formally. In this article, we have reviewed the results that have lead to the conclusion that the assessment of successful DSB repair can be the basis of reliable assays predictive of the clinical response to radiotherapy and some chemotherapeutic treatments. We have discussed a number of technical artifacts, the biases due to the extrapolation of data obtained in yeast and rodent model systems to the human situation and the variety of phenotypes observed in human cells and in particular: 1) the most recent techniques developed, based on immunofluorescence, which have revolutionized our understanding of the molecular events occurring early after irradiation but have also raised the crucial questions about the choice of techniques to assess DSB repair and their specificity for different steps of the repair process; 2) While the homologous recombination repair pathway is predominant in yeasts, its importance in human cells appears less obvious, and raises the problem that the existence of randomized repair events may produce many more errors in human cells than in small genome organisms; 3) the impairment of DSB repair is observed in a plethora of genetic diseases, leading to radiosensitivity, immunodeficiency and sometimes cancer-proneness, but the low frequency and the pleiotropism of such diseases makes difficult the development of a single predictive assay. Therefore, although complete DSB repair appears to be crucial for cell survival, further research is still needed to provide innovative techniques fro measuring repair which can be successfully transferred to the clinic and used to ensure the avoidance of deleterious side-effects to cancer therapies.; Parmi les nombreux dommages radio-induits de l'ADN, les cassures double-brin sont considérées aujourd'hui comme les lésions clés de l'effet létal des radiations ionisantes. Pourtant, cette conclusion, qui a toujours été intuitive pour les radiobiologistes, est le résultat d'un long et difficile processus de développements techniques et conceptuels et reste encore consensuelle plutôt que formellement démontrée. Dans cette revue, nous nous sommes efforcés de décrire les différentes étapes de la pensée et les résultats marquants qui permettent aujourd'hui d'affirmer que le succès de la réparation des cassures double-brin peut être effectivement à la base de tests fiables et de prédiction de la réponse clinique à la radiothérapie et à certaines chimiothérapies. Nous évoquerons notamment les biais artéfactuels des nombreuses techniques utilisées, les pièges dus à l'extrapolation des données obtenues sur les levures et les rongeurs ainsi que la variété des phénotypes rencontrés dans les cellules humaines : 1) en particulier, bien que les techniques d'immunofluorescence les plus récentes ont révolutionné l'image que l'on se faisait des événements radio-induits précoces, le choix de la technique de mesure des cassures double-brin semble conditionner l'observation sur des étapes très spécifiques de certaines voies de réparation ; 2) alors que la recombinaison homologue est prédominante chez les levures, son importance dans les cellules humaines apparaît toute relative et pose le problème de l'existence de voies de réparation s'effectuant au hasard qui pourraient produire beaucoup plus d'erreurs chez l'homme que dans les organismes à petits génomes ; 3) des dysfonctionnements de la réparation sont aujourd'hui observés dans de nombreuses maladies génétiques, conduisant à de fortes ou de faibles radiosensibilités, immunodéficience ou prédisposition au cancer, rendant ainsi illusoire la mise au pont d'un test prédictif unique. Ainsi, bien que les cassures double-brin jouent indubitablement un rôle important dans la mort radio-induite, les recherches doivent encore se poursuivre pour offrir aux cliniciens des outils puissants pour sécuriser le transfert clinique des approches innovantes et pour limiter les réactions suraiguës aux traitements anticancéreux.

International audience; XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation group C. The patient was unusual in presenting with an angiosarcoma of the scalp, treated by surgical excision and radiotherapy. Following 38 Gy in 19 fractions with 6 MEV electrons, a severe desquamation and necrosis of the underlying bone ensued, and death followed 4 years later. The cell line was correspondingly hypersensitive to the lethal effects of gamma irradiation. We had previously shown that this sensitivity could be discriminated from that seen in ataxia-telangiectasia (A-T). The cellular response to ultraviolet radiation below 280 nm (UVC) was characteristic of XP cells, indicating the second instance, in our experience, of dual cellular UVC and ionizing radiation hypersensitivity in XP. We then set out to evaluate any defects in repair of ionizing radiation damage and to verify any direct contribution of the XPC gene. The cells were defective in repair of a fraction of double strand breaks, with a pattern reminiscent of A-T. The cell line was immortalized with the vector pSV3neo and the XPC cDNA transfected in to correct the defect. The progeny derived from this transfection showed the presence of the XPC gene product, as measured by immunoblotting. A considerable restoration of normal UVC, but not ionizing radiation, sensitivity was observed amongst the clones. This differential correction of cellular sensitivity is strong evidence for the presence of a defective radiosensitivity gene, distinct from XPC, which is responsible for the clinical hypersensitivity to ionizing radiation. It is important to resolve how widespread ionizing radiation sensitivity is amongst XP patients.

Bleomycin is a cytotoxic antibiotic that generates DNA double-strand breaks (DSB) and DNA single-strand breaks (SSB). It is possible to introduce known quantities of bleomycin molecules into cells. Low amounts kill the cells by a slow process termed mitotic cell death, while high amounts produce a fast process that has been termed pseudoapoptosis. We previously showed that these types of cell death are a direct consequence of the DSB generated by bleomycin. Here, we use deglyco-bleomycin, a bleomycin derivative lacking the carbohydrate moiety. Although this molecule performs the same nucleophilic attacks on DNA as bleomycin, we show that deglyco-bleomycin is at least 100 times less toxic to Chinese hamster fibroblasts than bleomycin. In fact, deglyco-bleomycin treatment results in apoptosis induction. In contrast, however, deglyco-bleomycin was found to generate almost exclusively SSB. Our results suggest that more than 150 000 SSB per cell are required to trigger apoptosis in Chinese hamster fibroblasts and that SSB are 300 times less toxic than DSB. Taken together with previous studies on bleomycin, our data demonstrates that cells can die by apoptosis, mitotic cell death, or pseudoapoptosis, depending on the number of DNA breaks and on the ratio of SSB to DSB. © 2001 Cancer Research Campaign http://www.bjcancer.com

We have studied the intrinsic radiosensitivity, repair of potentially lethal damage (PLD) and the repair rate of radiation-induced DNA double-strand breaks (DSB) in 11 non-transformed human fibroblast cell lines, four of which were homozygous for the A-T mutation and two that were heterozygous (A-TH). All the experiments were done on cells in plateau phase of growth (97-99% of cells in G0/G1). With a dose of 30 Gy delivered at 4 degrees C, the A-T cell lines had faster repair rates of up to 6 h, after which the repair curve crossed that of the control so that the residual damage at 24 h was higher in the A-T cells. Irradiation at 37 degrees C at low dose rate 1 cGy.min-1) produced even more marked differences between the A-T cells and controls: the residual DSB level was always higher in A-T cells than controls at doses of 5-40 Gy, due to defective repair of a small fraction of DSB in A-T cells. The two protocols showed DSB repair rates for the A-TH cell lines that were intermediate between those of the A-T and control cells. There was a quantitative relationship between the residual DSB after irradiation at 37 degrees C and the intrinsic radiosensitivity, and with the extent of PLD repair. There were very few apoptotic cells in the non-transformed control and A-T cell line, both before and after irradiation. In combination, these result support the contention that the defective repair of DSB is a mechanism of the hypersensitivity linked to the A-T mutation.

The aim of this work was to measure simultaneously and in a quantitative manner double-strand breaks (DSBs), interphase chromosome breaks and cell lethality either immediately after irradiation, or at various times thereafter (up to 24 h), in cells of three nontransformed human fibroblast cell lines of widely different intrinsic radiosensitivity. We wished to assess initial damage, repair kinetics and residual damage at the DNA and the chromosome level, and to correlate these parameters with cell killing. We employed HF19 cells, a normal fibroblast cell line, AT2 cells, a radiosensitive cell line from a patient suffering from ataxia telangiectasia (AT), and 180BR cells, a radiosensitive cell line from a patient with no clinical symptoms of AT. AT2 and 180BR cells, in addition to being radiosensitive, also display a reduced ability to repair potentially lethal damage compared to HF19 cells. The yield of DSBs, as measured by pulsed-field gel electrophoresis, is similar in all three cell lines (slopes correspond to 1.6-1.7% Gy-1 of DNA-associated radioactivity released from the gel well into the lane). In contrast, residual DSBs measured 24 h after irradiation are almost zero for HF19 cells (0.1% confidence interval = 0-1.4%), but are 12.5% (+/- 2.3%) and 43.8% (+/- 1.2%) of those measured immediately after irradiation in AT2 and 180BR cells, respectively. Residual interphase chromosome breaks are 11.6% (+/- 1.6%), 29.7% (+/- 5.7%) and 41.4% (+/- 2.2%) of those measured immediately after irradiation in HF19, AT2 and 180BR cells, respectively. Neither the initial yield of DSBs nor that of excess interphase chromosome breaks can explain the differences in radiosensitivity between the three cell lines; however, there is a correlation between residual DSBs, rate of DSB rejoining at 24 h, residual interphase chromosome breaks on the one hand and cell survival on the other hand.

Using pulsed-field gel electrophoresis (PGFE), we measured DNA double-strand breaks (DSB) in a normal human fibroblast and in a cell line derived from a patient suffering from ataxia telangiectasia (AT), a syndrome associated with a hypersensitivity to ionizing radiation. Initial DSB levels assessed after irradiation at 4 degrees C are similar in both cell lines. The DSB repair rate was measured after 30 Gy delivered at 4 degrees C and followed by an incubation at 37 degrees C for 24 h. In AT cells, the DSB repair rate is faster between 0.5 and 9 h and slower between 9 and 24 h. In addition, the DSB levels were measured after irradiation at 37 degrees C at 0.01 Gy min-1 (5-40 Gy). The shape of the curves was curvilinear and a plateau was reached at 10 Gy in the control. After an irradiation at 37 degrees C, DSB levels were significantly higher in AT cells than in the normal fibroblast cells. A model was developed assuming that DSB induction is independent of temperature and that DSB repair rate is independent of dose-rate and dose. This model was used to predict the 37 degrees C DSB data on the basis of the 4 degrees C data. Experimental data and predictions are in agreement, thus validating the above assumptions. It is suggested that, even for extreme situations such as 30 Gy delivered at 4 degrees C or 30 Gy delivered at 37 degrees C at 0.01 Gy min-1, DSB induction and repair are identical. Our results could be interpreted assuming an heterogeneity of DSB. A small fraction of DSB is slowly repaired. This fraction is lower in control than in AT cells. By protracting repair time, the 37 degrees C low-dose rate experiments permit a cleaner distinction between AT and control cells.

A review of reports dealing with fittings of the data for repair of DNA double-strand breaks (DSBs) and excess chromosome fragments (ECFs) shows that several models are used to fit the repair curves. Since DSBs and ECFs are correleated, it is worth developing a model describing both phenomena. The curve-fitting models used most extensively, the two repair half-times model for DSBs and the monoexponential plus residual model for ECFs, appear to be too inflexible to describe the repair curves for both DSBs and ECFs. We have therefore developed a new concept based on a variable repair half-time. According to this concept, the repair curve is continuously bending and dependent on time and probably reflects a continuous spectrum of damage repairability. The fits of the curves for DSB repair to the variable repair half-time and the variable repair half-time plus residual models were compared to those obtained with the two half-times plus residual and two half-times models. Similarly, the fits of the curves for ECF repair to the variable repair half-time and variable half-time plus residual models were compared to that obtained with the monoexponential plus residual model. The quality of fit and the dependence of adjustable parameters on the portionmore » of the curve fitted were used as comparison criteria. We found that: (a) It is useful to postulate the existence of a residual term for unrepairable lesions, regardless of the model adopted. (b) With the two cell lines tested (a normal and a hypersensitive one), data for both DSBs and ECTs are best fitted to the variable repair half-time plus residual model, whatever the repair time range. 47 refs., 3 figs., 3 tabs.« less

Purposes: The term “radiosensitivity” appeared for the first time at the beginning of the 20th century, few years after the discovery of X-rays. Initially used by French and German radiologists, it illustrated the risk of radiation-induced (RI) skin reactions. From the 1950’s, “radiosensitivity” was progressively found to describe other features of RI response such as RI cancers or cataracts. To date, such confusion may raise legal issues and complexify the message addressed to general public. Here, through an historical review, we aimed to better understand how this confusion appeared. Methods: To support our historical review, a quantitative and qualitative wording analysis of the “radiosensitivity” occurrences and its derived terms was performed with Google books, Pubmed, Web of Science™ databases and in all the ICRP publications. Conclusions: While “radiosensitivity” was historically related to RI adverse tissue events attributable to cell death, the first efforts to quantify the RI risk specific to each organ/tissue revealed some different semantic fields that are not necessarily compatible together (e.g. adverse tissue events for skin, cataracts for eyes, RI cancer for breast or thyroid). To avoid such confusion, we propose to keep the historical definition of “radiosensitivity” to any clinical and cellular consequences of radiation attributable to cell death and to introduce the term “radiosusceptibility” to describe the RI cancers or any feature that is attributable to cell transformation.

International audience; Exposure to radiation is one of the main concerns for space exploration by humans. By focusing deliberately on the works performed on human cells, we endeavored to review, decade by decade, the technological developments and conceptual advances of space radiation biology. Despite considerable efforts, the cancer and the toxicity risks remain to be quantified: 1) the nature and the frequency of secondary heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response; 2) the diversity of radiation history of each astronaut and the impact of individual susceptibility make very difficult any epidemiological analysis for estimating hazards specifically due to space radiation exposure. 3) Cytogenetic data undoubtedly revealed that space radiation exposure produce significant damage in cells. However, our knowledge of the basic mechanisms specific to low-dose, to repeated doses and to adaptive response is still poor. The application of new radiobiological techniques, like immunofluorescence, and the use of human tissue models different from blood, like skin fibroblasts, may help in clarifying all the above items.