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Radiation response genotype and risk of differentiated thyroid cancer: a case-control analysis.

BACKGROUND: Radiation is the only clear etiologic agent for differentiated thyroid cancer (DTC). Understanding the factors affecting sensitivity to gamma radiation and susceptibility to DTC will be critical to early detection and prevention of DTC. HYPOTHESIS: Germline variants of double-strand break repair genes are markers of DTC risk. OBJECTIVE: Determine the frequency of common single nucleotide polymorphisms of genes of the double-strand break repair pathway in patients with DTC and cancer-free controls. STUDY DESIGN: Case-control study. METHODS: This study included 134 patients with DTC, 79 patients with benign thyroid lesions, and 166 cancer-free control subjects. To avoid ethnic confounding, all subjects were non-Hispanic whites. Genotype analyses were performed on DNA isolated from peripheral blood lymphocytes. Multivariate logistic regression analyses were performed to estimate the risk of DTC associated with each variant genotype. RESULTS: The XRCC3 18067T polymorphic allele was found significantly more commonly among the DTC cases than for the control subjects (P=.006). After multivariate adjustment, having the XRCC3 18067T allele was associated with an increased risk of DTC (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3 to 3.4; P = .004). In addition, there was a suggestion that the XRCC3 18067T polymorphic allele was more common among the patients with benign thyroid disease (P = .054), and the homozygous polymorphic genotype was associated with risk for benign thyroid disease (adjusted OR = 2.1; 95% CI = 0.9-4.9; P = .078). CONCLUSIONS: In this case-control analysis, the XRCC3 18067T polymorphism is associated with DTC risk. However, such work needs confirmation in larger studies.

Adolescent↗

The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid.

Folate is an essential nutrient that is involved in many metabolic pathways, including amino acid interconversions and nucleotide (DNA) synthesis. In genetically susceptible individuals and populations, dysfunction of folate metabolism is associated with severe illness. Despite the importance of folate, major gaps exist in our quantitative understanding of folate metabolism in humans. The gaps exist because folate metabolism is complex, a suitable animal model that mimics human folate metabolism has not been identified, and suitable experimental protocols for in vivo studies in humans are not developed. In general, previous studies of folate metabolism have used large doses of high specific activity tritium and 14C-labeled folates in clinical patients. While stable isotopes such as deuterium and 13C-labeled folate are viewed as ethical alternatives to radiolabeled folates for studying metabolism, the lack of sensitive mass spectrometry methods to quantify them has impeded advancement of the field using this approach. In this chapter, we describe a new approach that uses a major analytical breakthrough, Accelerator Mass Spectrometry (AMS). Because AMS can detect attomole concentrations of 14C, small radioactive dosages (nCi) can be safely administered to humans and traced over long periods of time. The needed dosages are sufficiently small that the total radiation exposure is only a fraction of the natural annual background radiation of Americans, and the generated laboratory waste may legally be classified non-radioactive in many cases. The availability of AMS has permitted the longest (202 d) and most detailed study to date of folate metabolism in a healthy adult human volunteer. Here we demonstrate the feasibility of our approach and illustrate its potential by determining empirical kinetic values of folate metabolism. Our data indicate that the mean sojourn time for folate is in the range of 93 to 120 d. It took > or = 350 d for the absorbed portion of small bolus dose of 14C-folic acid to be eliminated completely from the body.

Area Under Curve↗

A space radiation shielding model of the Martian radiation environment experiment (MARIE).

The 2001 Mars Odyssey spacecraft was launched towards Mars on April 7, 2001. Onboard the spacecraft is the Martian radiation environment experiment (MARIE), which is designed to measure the background radiation environment due to galactic cosmic rays (GCR) and solar protons in the 20-500 MeV/n energy range. We present an approach for developing a space radiation-shielding model of the spacecraft that includes the MARIE instrument in the current mapping phase orientation. A discussion is presented describing the development and methodology used to construct the shielding model. For a given GCR model environment, using the current MARIE shielding model and the high-energy particle transport codes, dose rate values are compared with MARIE measurements during the early mapping phase in Mars orbit. The results show good agreement between the model calculations and the MARIE measurements as presented for the March 2002 dataset.

Computer Simulation↗

Radiation therapy impairs endothelium-dependent vasodilation in humans.

OBJECTIVES: The objective of this study was to test the hypothesis that external-beam radiation induces a chronic impairment of endothelium-dependent vasodilation. BACKGROUND: Radiation therapy is used commonly in the treatment of cancer and is associated with an increased incidence of adverse vascular events related to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction. METHODS: Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before enrollment and ten healthy women were studied. Vascular ultrasonography was used to image both the artery exposed to radiation and the contralateral artery. Flow-mediated, endothelium-dependent vasodilation and endothelium-independent vasodilation to nitroglycerin of both axillary arteries were measured. RESULTS: Endothelium-dependent vasodilation was significantly impaired in the irradiated axillary arteries compared with the contralateral, nonirradiated arteries (-0.4 +/- 0.4% vs. 3.2 +/- 0.8% p < 0.001) and also compared with control subjects' arteries (-0.4 +/- 0.4% vs. 2.5 +/- 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arteries that received radiation compared with the contralateral arteries (3.8 +/- 0.5% vs. 2.0 +/- 0.4%, p < 0.05) and also compared with control arteries (3.8 +/- 0.5% vs. 2.5 +/- 0.4%, p < 0.05). CONCLUSIONS: External beam radiation therapy impairs endothelium-dependent vasodilation of conduit arteries, implicating a decrease in the bioavailability of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events.

Aged↗

Occupational radiation exposure to the surgeon.

Increased use of intraoperative fluoroscopy exposes the surgeon to significant amounts of radiation. The average yearly exposure of the public to ionizing radiation is 360 millirems (mrem), of which 300 mrem is from background radiation and 60 mrem from diagnostic radiographs. A chest radiograph exposes the patient to approximately 25 mrem and a hip radiograph to 500 mrem. A regular C-arm exposes the patient to approximately 1,200 to 4,000 mrem/min. The surgeon may receive exposure to the hands from the primary beam and to the rest of the body from scatter. Recommended yearly limits of radiation are 5,000 mrem to the torso and 50,000 mrem to the hands. Exposure to the hands may be higher than previously estimated, even from the mini C-arm. Potential decreases in radiation exposure can be accomplished by reduced exposure time; increased distance from the beam; increased shielding with gown, thyroid gland cover, gloves, and glasses; beam collimation; using the low-dose option; inverting the C-arm; and surgeon control of the C-arm.

Female↗

Mortality and morbidity of members of the British Nuclear Tests Veterans Association and the New Zealand Nuclear Tests Veterans Association and their families.

More than 20,000 British servicemen--many of them on their National Service, few of them volunteering for the tests, and most in their early twenties, some still boy soldiers in their teens--were required to 'participate' in the United Kingdom nuclear tests in Australia and Christmas Island in the 1950s and 1960s. 528 members of the New Zealand Navy were also present for one series of tests. There was also a Fijian Army contingent, which has been variously numbered between 100 and 500 men. An estimated 16,000 Australian servicemen and civilians were also involved in the tests at Maralinga and other sites. The men performed a wide range of duties, from highly technical preparations for the detonations to catering and clerical jobs. But whatever their role, they were all required to witness the detonations as part of their 'indoctrination' for the possibility of nuclear war. Most of them were required to line up on the beach, with their backs to the detonations and their hands over their eyes for the first minute or so. They were then allowed to turn around and look at the awesome sight as the mushroom cloud plumed thousands of feet into the air. Very few wore more than shorts and sandals during their time at the tests; only those who were thought to be at risk from radiation injury were issued with protective clothing and radiation dose badges. The UK government was sure that the troops, most of whom were standing within 20 km of the detonations and some of whom were present for 25 nuclear bomb blasts in as many weeks on Christmas Island, were not irradiated. The Ministry of Defence still routinely issues a document to nuclear veterans who feel that their illnesses were caused by the radiation they encountered when they were young men which states: The background [radiation] dose received by civilians and members of HM Forces serving at or off Christmas Island in the years 1956 to 1964 was only about 35% of that which they would have received on average had they remained, for that period of their lives, in the United Kingdom--that is, some 100 microsieverts per calendar month less at Christmas Island than in the United Kingdom. This sanguine view of the health burden borne by nuclear veterans and their families is not borne out by the data reported in this study of the health outcomes of the 2,500 men (2,200 UK, 238 New Zealand and 62 Fijian) on whom data are available to the present researcher. Thirty per cent of the men in this sample have already died, mostly in their fifties. Two-thirds of them died from cancers that are pensionable in the United States as presumptively radiogenic among nuclear veterans. About one in seven of the men in the sample of 1,014 who responded to the questionnaire circulated in late 1997 did not father any children after they returned from the weapons tests. Among the nearly 5,000 children and grandchildren of this group of more than a thousand veterans, there are 26 cases of spina bifida alone--more than five times the usual rate for live births in the UK. Nearly half the health problems among the offspring of the nuclear weapons tests veterans reported in this study consist of the same dermatological, musculoskeletal and gastrointestinal conditions from which many of the men have also suffered. Among the 2,261 children of 1,041 veterans, more than 200 skeletal abnormalities were reported, including more than 30 cases of short stature and 18 spinal problems, mostly curvature and scoliosis. More than 100 skin conditions were reported, mostly eczema and dermatitis, in many cases described as congenital. Over 50 of the children are already suffering from arthritis and similar conditions, although they are only now entering their thirties. Hip deformities were reported for 19 children and kneecap deformities for 14. More than 100 of the veterans' children reported reproductive difficulties; 24 women reported problems with their ovaries. This pattern of morbidity was repeated in the grandchildren, tho

Adolescent↗

Radiation effects on livestock: physiological effects, dose response.

Farm livestock show no measurable effects from being exposed to ionizing radiation unless the level is greatly in excess of the natural background radiation. Possible sources of ionizing radiation which might affect livestock or contribute to radioactivity in the food chain to humans are reactor accidents, fuel reprocessing plant accidents and thermonuclear explosions. Most data on ionizing radiation effects on livestock are from whole body gamma doses near the LD 50/60 level. However, grazing livestock would be subjected to added beta exposure from ingested and skin retained radioactive particles. Results of attempts to simulate exposure of the Hereford cattle at Alamogardo, NM show that cattle are more sensitive to ingested fallout radiation than other species. Poultry LD 50/60 for gamma exposure is about twice the level for mammals, and swine appear to have the most efficient repair system being able to withstand the most chronic gamma exposure. Productivity of most livestock surviving an LD 50/60 exposure is temporarily reduced and longterm effects are small. Livestock are good screeners against undesirables in our diet and with the exception of radiosotopes of iodine in milk, very little fission product radioactivity would be expected to be transferred through the food chain in livestock products for humans. Feeding of stored feed or moving livestock to uncontaminated pastures would be the best protective action to follow.

Animals↗

Radiation exposure to patient's skin during percutaneous coronary intervention for various lesions, including chronic total occlusion.

BACKGROUND: Radiation skin injuries have been reported as a result of various procedures, so in the present study the patients' entrance skin dose (ESD) during percutaneous coronary intervention (PCI) was evaluated. METHODS AND RESULTS: ESDs were assessed during 97 procedures (13 for chronic total occlusion (CTO), 14 for multivessel stenoses, 22 for single-vessel multiple stenoses, and 48 for single stenosis). The patients wore jackets that had 48 or 52 radiosensitive indicators placed on the back during the PCI procedures, with 8 other indicators placed on both upper arms. After the procedure, the color of the indicators was analyzed with a color measuring instrument, and the patients' ESDs were calculated from the color difference of the indicators. The average maximum ESDs of the patients were 4.5 +/- 2.8 Gy (median: 4.6 Gy) for CTO, 2.3 +/- 0.7 Gy (median: 2.4 Gy) for multivessel stenoses, 1.8 +/- 1.0 Gy (median: 1.5 Gy) for single-vessel multiple stenoses, and 1.4 +/- 0.9 Gy (median: 1.2 Gy) for single stenosis. CONCLUSIONS: Skin injury can occur during PCI, especially for CTO, so it is important to estimate each patient's ESD and attempt to reduce it.

Aged↗

Assessing unregulated ionizing radiation exposures of U.S. populations from conventional industries.

During the latter twentieth century, the public learned to fear perceived threats from emerging technologies. Concern about ionizing radiation became a persistent fear, causing protracted and often pointless debate. The twenty-first century offers new opportunities for this fear to cause public and political upset. Citizens and politicians know little about "normal" radiation exposures caused by conventional industries. This paper summarizes ionizing radiation exposure assessments of several such industries, showing they deliver multiples of background radiation annually to millions of people, with even higher subpopulation doses due to lognormally distributed exposures. Such information may be useful in educating the public and in supporting comparative assessments or other forms of research on potential sources of public radiation exposure in the twenty-first century. By exposing people to information about normal radiation, we may hope to avoid some unfortunate policies and unnecessary regulatory responses, while abating needless public fear during this technologically challenging century.

Humans↗

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

Adult↗

Temperature of the inflaton and duration of inflation from Wilkinson microwave anisotropy probe data.

If the initial state of the inflaton field is taken to have a thermal distribution instead of the conventional zero particle vacuum state then the curvature power spectrum gets modified by a temperature dependent factor such that the fluctuation spectrum of the microwave background radiation is enhanced at larger angles. We compare this modified cosmic microwave background spectrum with Wilkinson microwave anisotropy probe data to obtain an upper bound on the temperature of the inflaton at the time our current horizon crossed the horizon during inflation. We further conclude that there must be additional -foldings of inflation beyond what is needed to solve the horizon problem.

Journal Article↗

Medical aspects of power generation, present and future.

It can be seen that the radiation emissions of nuclear power plants are small indeed, compared to natural background radiation and other man-made sources of radiation. For example, the poulation is exposed to 100 times more radiation from television sets than from nuclear power reactors. The assumed risks to the people in this country from nuclear power reactors are also small compared to the normal risks which are tolerated in this society. The complete elimination of all hazards is a most difficult if not impossible task. If we need and desire a certain level of electrical energy, if we must choose between alternative sourves of the energy, then it is apparent that the total impact on our health from nuclear power generation of electricity, under normal operations and in consideration of catastrophic accident probabilities, is significantly less than that of continuing or increasing use of fossil fuels to generate electricity.

Abnormalities, Radiation-Induced↗

Radiation recall skin toxicity with bleomycin in a patient with Kaposi sarcoma related to acquired immune deficiency syndrome.

BACKGROUND: Radiation recall is a recurrence of acute toxicity within a previously quiescent radiation field that occurs with subsequent administration of chemotherapy. METHODS: A patient with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma (KS) who had radiation recall is reported. The patient was participating in a randomized prospective trial of radiation treatment regimens for KS. Each lesion was randomized to one of three possible radiation fractionation schemes. All lesions were photographed and measured before treatment with radiation. RESULTS: Two skin sites developed erythema and dry desquamation 18 days after completion of radiation therapy to a dose of 40 Gy in 20 fractions. These reactions took place after the second dose of bleomycin administered intravenously on a weekly basis. The reactions were exacerbated by oral etoposide therapy, which was started 4 days after the recall phenomenon was noted. Other cutaneous sites treated with 8 Gy in a single fraction and 20 Gy in ten fractions during the same time period showed no sign of recall skin toxicity. CONCLUSIONS: The authors believe this to be the first report of radiation recall toxicity after bleomycin therapy and of a radiation dose response related to this phenomenon. The potential for radiation recall toxicity should be considered in treatment decisions pertaining to patients with AIDS-associated KS.

AIDS-Related Opportunistic Infections↗

Risk calculations for hereditary effects of ionizing radiation in humans.

A prediction of the extent to which an additional dose of ionizing radiation increases the natural germ cell mutation rate, and how much such an increase will affect the health status of future human populations is part of the service that human geneticists are expected to offer to human society. However, more detailed scrutiny of the difficulties involved reveals an extremely complex set of problems. A large number of questions arises before such a prediction can be given with confidence; many such questions cannot be answered at our present state of knowledge. However, such predictions have recently been attempted. The 1988 report of the United Nations Scientific Committee for the Effects of Atomic Radiation and the fifth report of the Committee on Biological Effects of Ionizing Radiation of the US National Research Council have presented a discussion of the human genetics problems involved. Empirical data from studies on children of highly radiation-exposed parents, e.g. parents exposed to the atomic bombs of Hiroshima and Nagasaki, or parents belonging to populations living on soil with high background radiation, have been mentioned in this context. Whereas precise predictions are impossible as yet because of deficiencies in our knowledge of medical genetics at various levels, the bulk of the existing evidence points to only small effects of low or moderate radiation doses, effects that will probably be buried in the "background noise" of changing patterns of human morbidity and mortality.

Abnormalities, Radiation-Induced↗

[Results of the studies on radiation ecology and radiation biology at the Institute of Biology of Komi Science Center of Ural division of Russian Academy of Science (on 40th anniversary of the Department of Radiation Ecology)].

Information about the foundation and history of the Radiation Ecology Department and results of the researches on the effect of increased background radiation level on plant and animal populations, migration of radionuclides in natural biocoenosies with increased radiation level are presented.

Academies and Institutes↗

Natural language processing-based model to predict radiation pneumonitis in patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy: a retrospective cohort study.

BACKGROUND: Radiation pneumonitis (RP) remains a significant treatment-related toxicity in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) undergoing chemoradiotherapy (CRT). Most existing predictive models rely on static baseline demographic or dosimetry variables and lack real-time clinical applicability. We developed a novel predictive framework that integrates longitudinal symptom data extracted from clinical notes using natural language processing (NLP) with clinical and dosimetry features to improve early RP prediction. METHODS: We retrospectively identified 227 patients with locally advanced NSCLC treated with definitive CRT at a high-volume cancer center in the United States. We included all patients older than 18 years who were diagnosed between Jan 1, 2006, and Dec 31, 2022 with histologically or cytologically confirmed unresectable Stage 2 or 3 NSCLC and treated with conformal radiotherapy to a minimum dose of &#x2265;45 Gy with or without chemotherapy. Of these, 31 RP events were identified through manual adjudication using radiologic criteria and chart review. NLP was used to extract the temporal relationship of 16 pre-specified symptoms with treatment from over 100,000 clinical notes spanning pre- and during-treatment intervals. We trained and validated machine learning models on combinations of baseline clinical data, radiation dosimetry, and NLP-derived symptom features. Model performance was evaluated using a nested cross-validation framework, with an outer cross-validation loop reserved for performance assessment and an inner cross-validation loop used for model training and integration, and summarized using area under the receiver operating characteristic curve (AUC) and partial AUC (pAUC) at high specificity thresholds. Clinical utility was evaluated using decision curve analysis (DCA). FINDINGS: The best-performing model incorporated longitudinal NLP features and achieved a median AUC of 0.759 (90% confidence interval 0.753-0.766), significantly outperforming baseline models using only dosimetry (AUC 0.613) or clinical variables (AUC 0.635). NLP-based features such as cough trajectory, shortness of breath, and wheezing were among the most important predictors. Inclusion of NLP-derived symptom data improved early identification of high-risk patients, particularly in the clinically relevant high-specificity range (pAUC 0.021 vs. 0.010 for dosimetry alone). DCA showed that the calibrated MLP model provided greater net benefit than default strategies of treating all or no patients across clinically relevant threshold possibilities. INTERPRETATION: In this early work, NLP-based extraction of longitudinal symptoms from routine clinical documentation meaningfully enhances RP prediction in patients undergoing CRT for NSCLC. This approach leverages existing electronic health record infrastructure to deliver real-time, scalable, and interpretable risk estimates, offering a pathway toward potential early intervention and personalized toxicity management. The model and DCA requires external and prospective validation before clinical deployment; as such, future work should focus on this validation and integration into clinical decision support systems. FUNDING: AstraZeneca.

Chemoradiotherapy↗

Reactive oxygen species in cell responses to toxic agents.

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 microm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV alpha-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.

Antioxidants↗