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PubMed1991

Neoplastic diseases induced by chronic alpha-irradiation--epidemiological, biophysical and clinical results of the German Thorotrast Study.

The intravascular injection of the formerly used contrast medium Thorotrast--a colloidal suspension of thorium-dioxide--causes a chronic exposure to alpha-particles especially in the organs of the reticuloendothelial system. The German Thorotrast Study comprises 2326 Thorotrast patients and 1890 contemporary matched patients in the control group to be evaluated. 899 Thorotrast patients and 662 controls had clinical and biophysical follow-up examinations every two years since 1969. The recent most important results of the study are: A high excess rate of primary liver cancer (410/2) was observed beginning after the 15th year of exposure. 31% of the tumors are combined with cirrhosis and 6% with other neoplastic diseases. A clear (mean) dose rate effect relationship exists. The tumor frequency depends on the time of exposure or the cumulative dose to the liver respectively and not primarily on the age at injection. The lowest cumulative doses at 10 years before diagnosis of liver cancer were about 2 Gy. Risk estimates for liver cancer after 40 years of exposure are 500 malignant tumors per 10(4) person-Gy for men and 300 for women. A high excess rate exists also for leukaemias (excluding CLL) starting already 5 years after Thorotrast injection (39/4). The lowest cumulative doses to the red bone marrow at time of death were about 0.5 Gy. According to the present result, an excess rate can be expected for carcinomas of the extrahepatic bile ducts, pancreas, oesophagus, larynx, as well as Non-Hodgkin's lymphomas, bone sarcomas, plasmacytomas and mesotheliomas.

Adolescent↗
PubMed2002

The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data.

Chronic exposure to high LET radiation has been shown to cause liver cancer in humans based on studies of patients who received Thorotrast, a colloidal suspension of thorium dioxide formerly used as a radiological contrast agent, and on studies of Russian nuclear weapons workers exposed to internally ingested plutonium. Risk estimates for these exposures and specific subtypes of liver cancer have not been previously reported. Combining published data with tumor registry data pertinent to the Thorotrast cohorts in Germany, Denmark, Portugal, and Japan and to Russian workers, we generally found significantly elevated risks of three major histologic types of liver tumors: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and hemangiosarcoma (HS) for Thorotrast exposures. In contrast, HS was the only liver tumor significantly associated with the lower alpha-particle doses experienced by the Russian workers. Excess cases per 1,000 persons exposed to Thorotrast were similar for the three liver cancer subtypes but lower for plutonium exposure. Odds ratios (OR) of HS and CC for Thorotrast were from 26 to 789 and from 1 to 31 times higher than those for HCC, respectively. ORs of liver cirrhosis for Thorotrast exposure ranged from 2.7 (95% confidence interval (CI): 2.2-3.4) to 6.7 (5.1-8.7).

Alpha Particles↗
PubMed1981

Collision tumor of the frontal sinus: evidence of prior intrasinus instillation of thorotrast.

Carcinoma of the frontal sinus is relatively rare. We describe a case of two independent carcinomas, squamous cell and adenoid cystic, in the right frontal sinus region of a patient who received sinus irrigation with an unidentified, substance 30 years previously. Radioautography performed on sections of the tumor tissue revealed linear tracks of the type produced by thorium decay, strongly suggesting that the substance was thorotrast. In addition to being the first description of a "collision tumor" of the frontal sinus, the case would represent the first reported instance of frontal sinus carcinoma following intrasinus instillation of thorotrast.

Aged↗
PubMed2002

Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats.

In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues. We compared the tissue reactions in rats to the carcinogenicity of a tantalum metal (Ta), as a negative foreign-body control, and to a colloidal suspension of radioactive thorium dioxide ((232)Th), Thorotrast, as a positive radioactive control. DU was surgically implanted in the thigh muscles of male Wistar rats as four squares (2.5 x 2.5 x 1.5 mm or 5.0 x 5.0 x 1.5 mm) or four pellets (2.0 x 1.0 mm diameter) per rat. Ta was similarly implanted as four squares (5.0 x 5.0 x 1.1 mm) per rat. Thorotrast was injected at two sites in the thigh muscles of each rat. Control rats had only a surgical implantation procedure. Each treatment group included 50 rats. A connective tissue capsule formed around the metal implants, but not around the Thorotrast. Radiographs demonstrated corrosion of the DU implants shortly after implantation. At later times, rarifactions in the radiographic profiles correlated with proliferative tissue responses. After lifetime observation, the incidence of soft tissue sarcomas increased significantly around the 5.0 x 5.0 mm squares of DU and the positive control, Thorotrast. A slightly increased incidence occurred in rats implanted with the 2.5 x 2.5 mm DU squares and with 5.0 x 5.0 mm squares of Ta. No tumors were seen in rats with 2.0 x 1.0 mm diameter DU pellets or in the surgical controls. These results indicate that DU fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be detected with radiography in the muscles of rats.

Animals↗
PubMed1983

Human exposure to heavy metals. Rare earth pneumoconiosis in occupational workers.

A male subject exposed for many years to rare earth (RE)-containing fumes and dusts emitted from carbon arc lamps in photoengraving laboratories was investigated to rule out RE pneumoconiosis. While chest x-ray films showed a severe pulmonary fibrosis, clinical analysis showed obvious high RE concentrations in the pulmonary and lymph node biopsy specimens compared with the corresponding tissues of 11 unexposed subjects. In addition to other elements, levels of thorium (Th), which is generally present as an impurity of RE compounds, were also determined to estimate the radiation dose which may be involved in inducing pneumoconiosis. The results show that the levels of Th are more than two orders of magnitude lower than the maximum permissible concentration for occupational exposure to natural 232Th, suggesting that the long-term accumulation of RE in the lungs played a role in the pathogenesis of the observed pulmonary fibrosis of the worker.

Biopsy↗
PubMed1999

Biosorption of actinides from dilute waste actinide solution by egg-shell membrane.

Removal of radioactive elements from the effluent and waste aqueous solutions is an important problem. In previous laboratory batch experiments, hen egg-shell membrane (ESM) was stable as an insoluble protein and was very capable of binding heavy metal ions from aqueous solution. Batch laboratory pH profile, time dependency, and capacity experiments were performed to determine the binding of uranium (U) and thorium (Th) to ESM. Batch pH profile experiments indicated that the optimum pH for binding these actinides was approx 6.0 (U) or 3.0 (Th). The adsorption isotherms were developed at pH 5.0 (U) or 3.0 (Th) at 25 degrees C, and the adsorption equilibrium data fitted both Langmuir and Freundlich models. The maximum uptakes by the Langmuir model were about 240 mg U/g and 60 mg Th/g dry weight ESM. In addition, their adsorption capacities increased as salt concentration increased. ESM could also accumulate uranium from dilute aqueous solution by adjusting to the optimum pH. These results showed that ESM was effective for removing actinides from solution and would be useful in filtration technology to remove actinides from aqueous solution.

Actinoid Series Elements↗
PubMed1996

Dental fillings in Civil War skulls: what do they tell us?

This article discusses the dental techniques, methods and materials used in the South during the Civil War based on the dental restorations found in the skulls of four confederate soldiers. The skulls display a variety of dental filling materials, including thorium, lead, tin and tin amalgam. These materials were used at a time when more valuable materials, such as gold and silver, were not readily available in the South.

Dental Amalgam↗
PubMed2003

Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast.

Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P < 0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with >20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks.

Adult↗
PubMedDate not supplied

Erythroleukemia and gastric cancer following thorotrast injection.

A 63-year-old male, who had undergone angiography using thorium dioxide (Thorotrast) at the age of 15 for investigation of a giant hemangioma on his left thigh, developed anemia in September 1986 (47 yrs after the angiography). A diagnosis of erythroleukemia was made from a bone marrow study which showed 56.4% megaloblastoid erythroblasts and 12.8% myeloblasts. Autopsy revealed Thorotrast deposition in the liver, spleen, bone marrow, and lymph nodes, and monotonous proliferation of myeloblasts in the bone marrow. He also had differentiated tubular adenocarcinoma of the posterior wall of the stomach.

Adenocarcinoma↗
PubMed1997

Thorotrast and the liver--revisited.

BACKGROUND: Thorotrast, a radiological contrast medium that was widely used from 1928-1955 is a thorium dioxide colloid that has been neutralized and stabilized by colloid, composed of dextran. The major site of deposition is the reticuloendothelial system where it is retained for a long time. CASE REPORTS: Complications occurring late after exposure to thorotrast are described in two patients. RESULTS: One patient had angiosarcoma of liver metastatic to bone and bone marrow failure after a 43 year latency period. The other patient had a thorotrast granuloma and angiosarcoma of the liver after 22 year and 28 year latency periods respectively. CONCLUSIONS: Complications due to thorotrast appear to represent consequences of chronic alpha irradiation.

Aged↗
PubMed2003

Deaths from neoplasms and detection of radionuclides in excised human lungs in the Eordea Basin, Greece.

Lignite contains various trace-metal natural radioactive contaminants. In the Eordea Basin, the most important lignite field in Greece, the authors conducted a proportional mortality ratio (PMR) study that compared the mortality rates of individuals who lived in the basin vs. a control group who resided in the city of Kilkis, over a 30-yr period. The following information was used in the study: (a) municipal registrations of deaths from neoplasms during the period from 1971 to 2000, and (b) detection of radioactive substances in samples obtained from excised lungs of individuals living in Eordea Basin who suffered from neoplasm. The corresponding registrations of deaths from neoplasm of the inhabitants of Kilkis, a city located outside the Eordea Basin, formed the control group. A diachronic increase of the PMR was detected as a result of neoplasms and, particularly, as a result of lung cancer in Eordea Basin. However, the above ratio did not exceed the corresponding PMR recorded in Kilkis. In 20 lung samples obtained from patients who had lived in Eordea Basin, and in 19 lung samples from patients in Kilkis, the activity of the radionuclides of uranium and thorium radioactive decay series, potassium-40, and cesium-137 was not higher than expected. No statistically significant difference was found between the inhabitants of the 2 regions, thus it was concluded that the increase in respiratory-system neoplasms was likely associated with the high prevalence of smoking among the regions' inhabitants. In future studies, a longer observation period and examination of more cases will be necessary to further investigate a possible association between radionuclides and lung neoplasms in the Eordea Basin.

Aged↗
PubMed1977

Determination of uranium in human teeth, bones and tissues by the fission track method.

The uranium content of several human tooth, bone and soft tissue samples was determined by the fission tract method. The average uranium content in teeth, bones and soft tissues were 6.7, 8.4 and 64 ppb ash, respectively. The distribution of uranium in bones is less uniform than that of teeth, and the uranium content of soft tissues is generally higher than that of teeth and bone. The presence of thorium does not interfere with the uranium determination in most cases.

Bone and Bones↗
PubMed1978

[Determination of thorotrast amount deposited in patients (author's transl)].

Thorotrast amount deposited in patients, chiefly in the liver and the spleen, was determined with a NaI detector and a Computerised Axial Tomography (CT). In the measurement of the gamma-rays with the NaI detector, the geometry-factors, that are the distance from the detector to the source, the attenuation of the gamma-rays in the tissue and the shapes of the liver and the spleen, were studied, and the mean amount deposited in the organs was determined. In the measurement with CT, the relationship of CT-Number and the amount of thorium was got, and the localized amount and the distribution in the organ were measured.

Gamma Rays↗
PubMed1985

Cancer incidence among workers exposed to radon and thoron daughters at a niobium mine.

The aim of this study was to investigate the incidence of cancer among 318 male employees of a niobium mining company which was only operated between 1951 and 1965. Many of the workers, especially underground miners, were exposed to the daughters of radon and thoron and also to thorium. The accumulated doses to the workers from short-lived radon and thoron daughters in the mine atmosphere were assessed to be relatively low; up to 300 working-level months. During the follow-up period 1953-1981, 24 new cases of cancer were observed compared to an expected number of 22.8. Twelve cases of lung cancer had occurred versus 3.0 expected. Among the 77 miners, 9 cases of lung cancer were observed against 0.8 expected. Associations between the occurrence of lung cancer and exposure to alpha radiation and smoking were found. For the radon and thoron daughter exposure, about 50 excess cases per million person-years at risk per working-level month were observed.

Adult↗
PubMed1975

Hemangiosarcoma of the liver. Spectrum of morphologic changes and clinical findings.

Analysis of four cases of hemangiosarcoma of the liver and review of the literature indicate that these tumors are either predominantly cystic and fairly well differentiated or are more solid and poorly differentiated. Well-differentiated hemangiosarcomas may resemble peliosis hepatis or other benign conditions. The tumor was associated disseminated intravascular coagulation and fibrinolysis syndrome in one of our cases. One of our patients had received thorium dioxide (Thorotrast) but none seemed to have been exposed to arsenicals or to vinyl chloride.

Adult↗
PubMed2001

Alpha-particle carcinogenesis in Thorotrast patients: epidemiology, dosimetry, pathology, and molecular analysis.

We studied the alpha-radiation risks in patients who received injections of Thorotrast, an X-ray contrast medium used in Europe, Japan, and the United States from 1930 to 1955. Thorotrast was composed of thorium dioxide (ThO2) and Th-232, a naturally occurring radionuclide. Because the physical half-life of ThO2 is 14 billion years and Thorotrast is hardly eliminated from the body, tissues in which it was deposited are irradiated by alpha-radiation for the entire lifetime of the subject. The dosimetry of Thorotrast patients is very complicated, but currently its reliability is quite high compared with other irradiated populations. The major causes of the death of Thorotrast patients are liver cancer, liver cirrhosis, leukemia, and other cancers. Three histologies of liver cancer are found: cholangiocarcinoma, hepatocellular carcinoma, and angiosarcoma. Although cholangiocarcinoma is the most frequent, angiosarcoma is characteristic of alpha-radiation. Among blood neoplasms with a higher incidence of increase than the general population, erythroleukemia and myelodysplastic syndrome were remarkable. Thorotrast patients exhaled a high concentration of radon (Rn-220), a progeny of Th-232, but no excesses of lung cancer in the patients of Japan, Germany, and Denmark were reported. Mutation analyses of p53 genes and loss of heterozygosity (LOH) studies at 17p locus were performed to characterize the genetic changes in Thorotrast-induced liver tumors. Interestingly, LOH, supposedly corresponding to large deletions was not frequent; most mutations were transitions, also seen in tumors of the general population, suggesting that genetic changes of Thorotrast-induced cancers are mainly delayed mutations, and not the result of the direct effects of radiation.

Adult↗
PubMed1975

Comparative study of abiogenesis of cysteine and other amino acids catalyzed by various metal ions.

The present work pertains to the study of the influence of nickel, cobalt, thorium, vanadium, molybdate, ferrous ions on the formation of cysteine which is synthesized abiogenically together with other amino acids in sterilized aqueous mixtures of ammonium thiocyanate, formaldehyde, potassium dihydrogen phosphate, calcium acetate, and biological minerals after irradiating by artificial light. The effect of these catalysts on cysteine formation was of the order: Fe++ greater than Mo++ greater than Th++++ greater than V++ greater than Co++ greater than Ni.

Acetates↗
PubMed2002

The use of secondary ion mass spectrometry (SIMS) to evaluate internal contamination.

Secondary ion mass spectrometry (SIMS) permits the detection of stable and radioactive elements in microvolume. Based on the ablation of specimens by ion bombardment, this mass spectrometry method allows a rapid assessment of trace elements in biological samples and enables accurate isotopic ratio determination. In this work, an application of SIMS in studies involving element microdistribution is illustrated on the basis of analyses of duodenal tissue sections from rats contaminated with either cerium or thorium. For this purpose, tests are performed with SIMS to analyze tissue sections obtained 12, 24 and 48 hr after contamination. In this report, strengths and limitations of SIMS are pointed out as an important tool in biological research.

Animals↗