Protracted Exposure Research Articles

Toxicology of Repeated Iodine Thyroid Blocking in Adult Rat

Radioactive iodines emitted following nuclear accidents are responsible for the dramatic increase of the late-onset thyroid cancer. Until the Fukushima disaster, a single dose of potassium iodide (KI) has been considered as an efficient countermeasure. Indeed, recently it has been suggested that repeated administration of KI may be necessary to ensure adequate protection in case of protracted exposure. Whereas, the effect of a single dose of KI has largely been studied ensuring its safety, studies regarding adverse effects of repeated iodine thyroid blocking (ITB) administration are scarce. Our objective was to assess the long term overall impact of KI in adult rats after repeated intake. Adult Wistar rats were subjected to either KI or saline solution over eight days. Biochemical homeostasis, hormones level, autoimmunity status, thyroid morphology and thyroid transcriptome profile were analyzed thirty days after the discontinuation of KI administration. Biochemical parameters, plasma levels of TSH; thyroid hormones; anti-TPO and anti-Tg did not differ between treated and control rats, the thyroid histology was not affected by the treatment and no long term transcriptome signature attributable to the treatment was noticed. Based on these data, we conclude the safety of repeated KI intake in adult rats; these data are prominent and may contribute to the ongoing development of KI guidelines and marketing authorization.

Ghrelin is a persistent biomarker for chronic stress exposure in adolescent rats and humans

Prolonged stressor exposure in adolescence enhances the risk of developing stress-sensitive mental illnesses, including posttraumatic stress disorder (PTSD), for many years following exposure cessation, but the biological underpinnings of this long-term vulnerability are unknown. We show that severe stressor exposure increased circulating levels of the hormone acyl-ghrelin in adolescent rats for at least 130 days and in adolescent humans for at least 4.5 years. Using a rodent model of longitudinal PTSD vulnerability in which rodents with a history of stressor exposure during adolescence display enhanced fear in response to fear conditioning administered weeks after stressor exposure ends, we show that systemic delivery of a ghrelin receptor antagonist for 4 weeks surrounding stressor exposure (2 weeks during and 2 weeks following) prevented stress-enhanced fear memory. These data suggest that protracted exposure to elevated acyl-ghrelin levels mediates a persistent vulnerability to stress-enhanced fear after stressor exposure ends.

Assessing the health effects associated with occupational radiation exposure in Korean radiation workers: protocol for a prospective cohort study

IntroductionThe cancer risk of radiation exposure in the moderate-to-high dose range has been well established. However, the risk remains unclear at low-dose ranges with protracted low-dose rate exposure, which is...

When are foliar anthocyanins useful to plants? Re-evaluation of the photoprotection hypothesis using Arabidopsis thaliana mutants that differ in anthocyanin accumulation

There is strong empirical evidence that foliar anthocyanins assist in protecting chloroplasts from potentially damaging effects of supernumerary photons. Nevertheless, around 30% of published reports failed to uncover any photoprotective advantage of red pigmentation. To understand why anthocyanins are evidently more useful in some situations than in others, we compared the stress responses of wild type (Col-0) Arabidopsis thaliana, which had only trace amounts of foliar anthocyanins, with those of the anthocyanin-rich pap1-D mutant, and, in some experiments, the anthocyanin-deficient ttg1-1. We recorded effects of light quality, light intensity, air temperature, and duration of exposure on quantum yields of photosystem II (ΦPSII) in leaves of different ages, and compared pigment profiles before and after treatment. Although similar in anatomy, chlorophyll content, and xanthophyll cycle activity, pap1-D was photoinactivated less than Col-0, but only when given at least 2 h exposure to saturating light at 10 °C. Differences between the responses of red and green leaves were greatest in older plants that were given protracted exposures to high fluxes of cool-white light (5600 K) at chilling temperatures, the decline in ΦPSII being inversely proportional to foliar anthocyanin concentration. Anthocyanins were more abundant in Col-0 and pap1-D after treatment, especially acylated forms for which the absorption spectrum matched the action spectrum for photoinhibition. The quality, intensity and duration of light stress profoundly influence the degree of photoprotection afforded by foliar anthocyanins. Photoabatement by anthocyanins provides a functional advantage only when the capacity for thermal energy dissipation is exceeded by the need to quench excess light.

Ionizing radiation does not impair the mechanisms controlling genetic stability during T cell receptor gene rearrangement in mice

Purpose: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation.Materials and methods: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0.1) or intermediate/high (0.2–1 Gy) doses of radiation either by acute X-rays exposure or protracted exposure to low dose-rate γ-radiation was used to analyse by PCR the presence of illegitimate TR gene rearrangements.Results: Radiation exposure does not increase the onset of TR gene trans-rearrangements in irradiated mice. In mice where it happens, trans-rearrangements remain sporadic events in developing T lymphocytes.Conclusion: We concluded that low dose/low dose rate ionizing radiation (IR) exposure does not lead to widespread inactivation of ATM-dependent mechanisms, and therefore that the mechanisms enforcing genetic stability are not impaired by IR in developing lymphocytes and lymphocyte progenitors, including BM-derived hematopoietic stem cells, in low dose/low dose rate exposed mice.

Direct adjustment for confounding by smoking reduces radiation-related cancer risk estimates of mortality among male nuclear workers in Japan, 1999–2010

A causal relationship between protracted exposure to low-dose rate radiation and health effects remains unclear despite extensive international studies of nuclear workers. One potential reason is that radiation epidemiological studies that adjust for tobacco smoking, which heavily influences mortality, have been limited. In the present study, we examined radiation-related cancer risk by directly assessing the possible confounding effect of smoking, using data from two questionnaire surveys performed among Japanese nuclear workers in 1997 and 2003. Mortality follow-up was carried out for 71 733 male respondents for an average of 8.2 years during the observation period of 1999–2010. The mean cumulative dose was 25.5 mSv at the end of the follow-up period. Estimates of excess relative risk per Sv (ERRs/Sv) were obtained by Poisson regression. By adjusting for smoking directly on the basis of a linear dose-response model, we quantified the confounding effects of smoking on radiation risks. Statistically significant ERRs/Sv were found for all causes, all diseases, all non-cancer diseases, and liver cancer: 0.97 (90% confidence interval: 0.23, 1.78), 1.32 (0.40, 2.34), 1.87 (0.47, 3.49), and 4.78 (0.09, 11.68), respectively, without adjustment for smoking. However, the ERRs/Sv were no longer statistically significant after adjustment for smoking: 0.45 (−0.22, 1.19), 0.77 (−0.08, 1.72), 1.28 (−0.03, 2.79), and 3.89 (−0.46, 10.34), respectively. The ERRs/Sv for all cancers excluding leukaemia and lung cancer were not significant before adjustment for smoking, but declined after adjustment for smoking. The present study demonstrates that in this cohort of workers, smoking heavily distorts radiation risk estimates of mortality. The possibility of confounding by smoking depends on how strongly smoking is correlated with radiation exposure. If a correlation between smoking and radiation dose is suggested, smoking is an important confounder when assessing the radiation and health risks.

Nanofibers of resorcinol-formaldehyde for effective adsorption of As (III) ions from mimicked effluents.

In the present study, the core-shell structured RF/PVA nanofibers have been developed and used for the adsorption of As3+ ions from the mimicked liquid effluents. Efficient-facile fabrication of the structured nanofibers (300-417nm diameter) was accomplished using facile electrospinning technique. Chi parameter (χ = 25.56) and free energy of mixing (Emix = 17.19kcal/mol) calculated via molecular dynamics simulations depicted compatibility of the polymeric system resulting supermolecular core-shell nanofibers, whose adsorption results were also supported by the FE-SEM, FT-IR, and UV-VIS spectroscopy analysis. The adsorption analysis was performed using both linear and non-linear regression methods, for kinetic models and adsorption isotherms. The developed nanofibers demonstrated an adsorption capacity of 11.09mg/g at a pH of 7, and an adsorption efficiency of 97.46% on protracted exposure, which is even adaptable at high temperatures with 93.1% reclamation. FE-SEM analysis and FT-IR spectra confirm the adsorption of As (III) ions on RF/PVA nanofibers and the presence of embedded hydrophilic oxygen sites for metal ion adsorption. The developed RF/PVA nanofibers demonstrate scalability in fabrication, low-cost, recycling, and less solid waste generation, depicting the large-scale applicability in removing arsenic ions from effluent waste. Graphical Abstract ᅟ.

The Effect of Protracted Exposure to Radiation on Liver Injury: A Cohort Study of Industrial Radiographers in Xinjiang, China.

Background: At present, a large number of studies indicate that high dose ionizing radiation exposure is an important risk factor for liver damage. Whether protracted exposure to low external doses of ionizing radiation could induce liver injury is unclear. The aim of this study was to assess the risk of liver injury following protracted exposure to occupational radiation compared to a group of unexposed workers. Methods: A three-year cohort study was initiated in Xinjiang, China in 2010 and included 508 industrial radiographers and 2156 unexposed workers. The incidence of liver injury was assessed clinically based on the evaluation of alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. Logistic regression was used to examine whether radiation is a risk factor for liver injury. Results: Compared with the unexposed group, protracted radiation exposure was found to be a risk factor for liver injury. Sex, age at baseline and alcohol consumption were not associated with liver injury. However, hypertension was a risk factor for liver injury. The association between cumulative recorded radiation dose and liver injury was not found in this study. Conclusions: These findings indicate that protracted exposure to radiation is a risk factor for liver injury.

Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS).

There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

The Writing "Crisis": Vol. 41, No. 1, November 1978

The Writing "Crisis"Vol. 41, No. 1, November 1978 Leo Marx Perhaps I should admit, at the outset, that I am not a full-fledged member of the English-teaching profession. Although I have belonged to English departments during most of my academic life, I hold no degree in English. But in any case I would like to identify myself with certain of the current concerns of the profession. A few weeks ago, I was sitting on a committee interviewing candidates for the directorship of a university writing program. One candidate, himself the director of such a program, kept referring to "the crisis." Finally, one member of the committee, with some exasperation, asked, "By the way, what crisis are you talking about?" "Why, of course," the candidate responded, "the crisis in English composition." This "crisis," we all know, is a result of the recent discovery by people at Newsweek, Time, and The New York Times, that many young Americans, even after protracted exposure to the classroom teaching of English, are still unable to write the language. Not only are they unable to write, but their skill often declines during four years of higher learning at some of our most prestigious universities. We also know that this so-called crisis is a variant of another a few years back when the same publicists discovered that Johnny couldn't read. My sense is that the present crisis—which is a name for our difficulty in helping the young to think clearly and efficiently—is inseparable from other crises of recent years—the much larger socioeconomic and political crisis of our society. I don't mean to say that there isn't much yet to be done by way of improving instruction in writing and reading—what is now called "the basics"—but I also think there is no excuse for anyone in the profession adopting the Time/Newsweek talk about "the crisis" in English composition as if it might be a merely technical, professional problem susceptible to solutions by pedagogical experts. But how are we to relate the situation in English composition to the veritable cataclysm of crises this country went through in the era of Vietnam and Watergate? I want to consider the relationship between the low status of the profession nowadays and our tendency, as teachers, to deny or ignore larger social issues. When I speak of the profession's "low status," incidentally, I do not refer primarily to its economic but rather to its moral status as measured by the public respect it enjoys (or fails to enjoy) as compared [End Page 206] with other professions, and as compared with teachers of other academic subjects. That status, as you know, is not very high these days, and when it rises it usually does so for the wrong reasons. Like other groups which have suffered from public contempt or neglect, the English profession has reason to change the prevailing view of itself. One way to improve the status of the profession, I would suggest, is to bear down on the precise character of the relation between the degradation of language and the degradation of institutions, of people, in this society. Although it can be grossly misleading to speak of a "crisis" in English composition and literary studies, it is a fact that many intelligent Americans only now are becoming aware of the decline in language competency of the young. While that awareness doesn't necessarily constitute a crisis, it could provide an opening, a chance to educate the public about these matters, and at the same time, provide an opportunity to raise the moral status of the profession. This means—or so I shall be arguing—that we must address ourselves to issues of language education across the whole spectrum, from elementary education through college. We must open organizational as well as pedagogical or programmatic lines of communication with other teachers and professionals concerned with literature and language. And the reason for this, most simply stated, is that the English classroom is an arena of cultural politics. That what happens in the English classroom is closely bound up with the political health of the society is by no means a...

Populations Living near the Semipalatinsk Test Site: A New Cohort for Assessing Health Effects from Protracted Exposures to Low-to-moderate Doses of Radiation

Populations Living near the Semipalatinsk Test Site: A New Cohort for Assessing Health Effects from Protracted Exposures to Low-to-moderate Doses of Radiation

Benchmark dose analyses of multiple genetic toxicity endpoints permit robust, cross-tissue comparisons of MutaMouse responses to orally delivered benzo[a]pyrene

Genetic damage is a key event in tumorigenesis, and chemically induced genotoxic effects are a human health concern. Although genetic toxicity data have historically been interpreted using a qualitative screen-and-bin approach, there is increasing interest in quantitative analysis of genetic toxicity dose–response data. We demonstrate an emerging use of the benchmark dose (BMD)-approach for empirically ranking cross-tissue sensitivity. Using a model environmental carcinogen, we quantitatively examined responses for four genetic damage endpoints over an extended dose range, and conducted cross-tissue sensitivity rankings using BMD100 values and their 90% confidence intervals (CIs). MutaMouse specimens were orally exposed to 11 doses of benzo[a]pyrene. DNA adduct frequency and lacZ mutant frequency (MF) were measured in up to 8 tissues, and Pig-a MF and micronuclei (MN) were assessed in immature (RETs) and mature red blood cells (RBCs). The cross-tissue BMD pattern for lacZ MF is similar to that observed for DNA adducts, and is consistent with an oral route-of-exposure and differences in tissue-specific metabolism and proliferation. The lacZ MF BMDs were significantly correlated with the tissue-matched adduct BMDs, demonstrating a consistent adduct conversion rate across tissues. The BMD CIs, for both the Pig-a and the MN endpoints, overlapped for RETs and RBCs, suggesting comparable utility of both cell populations for protracted exposures. Examination of endpoint-specific response maxima illustrates the difficulty of comparing BMD values for a fixed benchmark response across endpoints. Overall, the BMD-approach permitted robust comparisons of responses across tissues/endpoints, which is valuable to our mechanistic understanding of how benzo[a]pyrene induces genetic damage.

Comparison of Toxicity and Recovery in the Duodenum of B6C3F1 Mice Following Treatment with Intestinal Carcinogens Captan, Folpet, and Hexavalent Chromium.

High concentrations of hexavalent chromium (Cr(VI)), captan, and folpet induce duodenal tumors in mice. Using standardized tissue collection procedures and diagnostic criteria, we compared the duodenal histopathology in B6C3F1 mice following exposure to these 3 carcinogens to determine whether they share similar histopathological characteristics. B6C3F1 mice (n = 20 per group) were exposed to 180 ppm Cr(VI) in drinking water, 12,000 ppm captan in feed, or 16,000 ppm folpet in feed for 28 days. After 28 days of exposure, villous enterocyte hypertrophy and mild crypt epithelial hyperplasia were observed in all exposed mice. In a subset of mice allowed to recover for 28 days, duodenal samples were generally indistinguishable from those of unexposed mice. Changes in the villi and lack of observable damage to the crypt compartment suggest that toxicity was mediated in the villi, which is consistent with earlier studies on each chemical. These findings indicate that structurally diverse agents can induce similar (and reversible) phenotypic changes in the duodenum. These intestinal carcinogens likely converge on common pathways involving irritation and wounding of the villi leading to crypt regenerative hyperplasia that, under protracted high-dose exposure scenarios, increases the risk of spontaneous mutation and tumorigenesis.

Circulatory disease in French nuclear fuel cycle workers chronically exposed to uranium: a nested case–control study

ObjectivesThere is growing evidence of an association between low-dose external γ-radiation and circulatory system diseases (CSDs), yet sparse data exist about an association with chronic internal uranium exposure and the...

Nasal Trigeminal Perception of Two Representative Microbial Volatile Organic Compounds (MVOCs): 1-Octen-3-ol and 3-Octanol—a Pilot Study

Nasal symptoms can be associated with indoor mold overgrowth, even absent allergic sensitization. An alternative pathogenic mechanism—mucous membrane irritation by microbial volatile organic compounds (MVOCs)—has been proposed. We conducted a pilot human study of nasal irritation by two MVOCs, 1-octen-3-ol and 3-octanol, hypothesizing that the former would show greater irritant potency based upon the compounds’ relative irritant potencies in rodents. Serial dilutions of the test compounds were prepared in odorless mineral oil vehicle, with headspace vapor concentrations documented by gas chromatography. Eight-step dilution series (with ascending concentration ratios ~ 1.34) were prepared. A nasal lateralization protocol was utilized. Ten subjects (seven females), aged 23–69, were each tested on four separate days, with each test compound being presented twice in alternating/counterbalanced order over the four testing days. Individual lateralization thresholds for a given compound, taken as dilution step, were averaged across subjects. Eight subjects were reliably able to lateralize stimuli for one or both test compounds. Among the 32 testing sessions completed by these eight subjects, 1-octen-3-ol was successfully lateralized in 15/16 and 3-octanol in 11/16. The mean dilution step at threshold was 3.125 for 1-octen-3-ol and 2.58 for 3-octanol. When presented as brief (~ 4 s.) stimuli, high concentrations of identified MVOCs can act as nasal mucosal irritants. Both detectability and repeatability, but not absolute (ppm) thresholds, exhibited compound-specific trends consistent with animal experimental data. Studies involving more protracted exposures with larger sample sizes may yield more realistic irritant threshold estimates. At sufficiently high concentrations, MVOCs can produce nasal irritation in humans.

Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells

Despite numerous observations linking protracted exposure to low-dose (LD) radiation and leukemia occurrence, the effects of LD irradiation on hematopoietic stem cells (HSCs) remain poorly documented. Here, we show that adult HSCs are hypersensitive to LD irradiation. This hyper-radiosensitivity is dependent on an immediate increase in the levels of reactive oxygen species (ROS) that also promotes autophagy and activation of the Keap1/Nrf2 antioxidant pathway. Nrf2 activation initially protects HSCs from the detrimental effects of ROS, but protection is transient, and increased ROS levels return, promoting a long-term decrease in HSC self-renewal. Invivo, LD total body irradiation (TBI) does not decrease HSC numbers unless the HSC microenvironment is altered by an inflammatory insult. Paradoxically, such an insult, in the form of granulocyte colony-stimulating factor (G-CSF) preconditioning, followed by LD-TBI facilitates efficient bone marrow transplantation without myeloablation. Thus, LD irradiation has long-term detrimental effects on HSCs that may result in hematological malignancies, but LD-TBI may open avenues to facilitate autologous bone marrow transplantation.

Neurotransmitter Switching Regulated by miRNAs Controls Changes in Social Preference

Changes in social preference of amphibian larvae result from sustained exposure to kinship odorants. To understand the molecular and cellular mechanisms of this neuroplasticity, we investigated the effects of olfactory system activation on neurotransmitter (NT) expression in accessory olfactory bulb (AOB) interneurons during development. We show that protracted exposure to kin or non-kin odorantschanges the number of dopamine (DA)- or gamma aminobutyric acid (GABA)-expressing neurons, withcorresponding changes in attraction/aversion behavior. Changing the relative number of dopaminergic and GABAergic AOB interneurons or locally introducing DA or GABA receptor antagonists alters kinship preference. We then isolate AOB microRNAs (miRs) differentially regulated across these conditions. Inhibition of miR-375 and miR-200b reveals that they target Pax6 and Bcl11b to regulate the dopaminergic and GABAergic phenotypes. The results illuminate the role of NT switching governing experience-dependent social preference. VIDEO ABSTRACT.

The untold story of the scorching sun—A wake up call for sun protection

Despite extensive warnings from health authorities regarding the dangers of direct sunlight exposure, most people still turn to sun bathing to get a golden tan. Unfortunately, that pleasant tan appearance is often lost because of over exposure to sunlight, resulting in painful red sunburns.In this paper we are reporting a case with significant sunburn injuries that required hospitalization and treatment in a burn center. Concurrently a pilot study was conducted to assess the knowledge about sun protection among the adult population and the results are discussed. The results obtained from the study revealed the lack of knowledge regarding sun protection and sun seeking behaviour among the responders.Deeper burns are rarely caused by direct sunlight exposure and are underreported in literature. Despite extensive health education and warnings, there are significant numbers of sunburn injuries reported annually. On most occasions, these are superficial and are in the form of erythema. Nonetheless, the public is unaware of the impending risks of developing deep sunburn injuries that can occur especially during protracted holiday exposures. Therefore, it is crucial to escalate public awareness and to implement preventive measures to reduce the short and long-term risks of sun exposure.

Protective effects of curcumin co-treatment in rats with establishing chronic variable stress on testis and reproductive hormones

Protracted and repeated exposure to chronic variable stress (CVS) may lead to reproductive dysfunction. It is a basic cause of male infertility. Curcumin (CUR) is an active fraction of turmeric that used in traditional Chinese medicine. CUR represents various pharmacological activities. The purpose of this study was to determining the effects of CUR on testis and testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in rats with establishing chronic variable stress. Twenty-one adult male Sprague-Dawley rats were divided into three groups: 1) control, 2) CVS and 3) CVS+ CUR (100 mg/kg/day dissolved in 0.5 mL of olive oil). All of the animals in control, CVS, and CVS+CUR groups were sacrificed after 15 days. Testosterone, FSH, LH, and testis damage were evaluated. Significant changes in the normal range of testosterone, FSH, LH serum levels and seminiferous tubule apoptotic cells were detected in CVS group compared to the control rats (p=0.02). These parameters changed to a less extent in CVS+CUR animals compared to the CVS rats (p=0.02). Our findings propose that curcumin might have curative potential on the reproductive system function and its impairment. It's regulated by stress and reproductive-related hormones.

Mortality in the French cohort of nuclear workers

Populations of nuclear workers are particularly relevant to study health effects of protracted exposures to low doses at low dose-rates of ionizing radiation. In France, a cohort of nuclear workers employed by the Commissariat a l'energie atomique et aux energies alternatives (CEA), AREVA Nuclear Cycle (AREVA NC), or Electricite de France (EDF), and badge-monitored for external radiation exposure, has been followed-up for several decades. Annual exposure to penetrating photons was reconstructed for each worker. Standardized mortality ratios were calculated using national mortality rates as the reference. Estimates of radiation dose-mortality associations were obtained using linear excess relative risk models. Mortality of 59 004 workers was followed-up between 1968 and 2004, for an average of 25 years. The mean cumulative photon Hp (10) dose was 18.4 mSv in the whole cohort (median value: 2.1 mSv) and 25.7 mSv among exposed workers. At the end of the follow-up, workers were 56 years old on average and 6310 workers had died. A strong healthy worker effect was observed. Estimated dose-risk relationships were consistent with those from other worker studies for all solid cancers and leukaemia excluding chronic lymphocytic leukaemia, but remained associated to a large uncertainty. This cohort is the most informative study ever conducted in France among nuclear workers.