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At least 667 records · Page 37Linked to original sources
PubMed1995

p53 mutations in primary hepatic angiosarcomas not associated with vinyl chloride exposure.

Angiosarcomas of the liver are rare, malignant cancers composed of neoplastic blood vessels. Human hapatic angiosarcomas have been associated with liver cirrhosis or exposure to vinyl chloride, Thorotrast or arsenic. A recent analysis of six hepatic angiosarcomas associated with vinal chloride exposure found three mutations and all were A:T --> T:A transversions, which are otherwise uncommon in human cancers. To test the specificity of this mutation spectrum, we analyzed 21 hepatic angiosarcomas not associated with vinyl chloride exposure. Four cases were exposed to Thorotrast, none had a history of arsenic exposure and the rest were sporadic. Exons 5-8 of the p53 gene were amplified by polymerase chain reaction, and the products were sequenced directly. Two G:C --> A:T transitions were found in two tumors: TGCstop in codon 136. Neither mutation was associated with Thorotrast exposure. These data indicate that p53 mutations are uncommon in sporadic hepatic angiosarcomas (2/21, 9%), and the mutational profile is consistent with endogenous mechanisms. Both features support the evidence linking vinyl chloride exposure to hepatic angiosarcomas containing an increased frequency of p53 mutations with a mutational spectrum (i.e. A:T --> T:A transversions) characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride.

Adult↗
PubMed1997

p53 gene mutation analysis in tumors of patients exposed to alpha-particles.

The p53 gene was examined for point mutations in archived, alpha-radiation-associated lung and liver cancers. Lung tumors of 50 uranium miners in Germany were screened by restriction fragment length analysis for the putative hotspot mutation at codon 249 (Arg-->Met) previously detected in a significant fraction of miners from the Colorado Plateau, USA. This mutation has been proposed as a marker of radon exposure. None of the tumors we examined harbored the hotspot mutation. Five of the 50 tumors, however, did indeed harbor exon 7 mutations, as determined by subsequent mutation analysis of exon 7. These mutations were dispersed among various codons and may be attributable to heavy tobacco smoking in this cohort. In support of this interpretation, we found no mutations in exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by injection of Thorotrast, an alpha-emitting radiocontrast agent. We propose that if the p53 tumor suppressor gene is a target for the carcinogenic action of alpha-particle radiation, loss of suppressor function may occur preferentially by mechanisms such as intrachromosomal deletions, rather than by base substitution mutations.

Aged↗
PubMed1989

Cancer among epileptic patients exposed to anticonvulsant drugs.

Cancer incidence among 8,004 patients hospitalized for epilepsy between 1933 and 1962 in the Filadelfia treatment community in Denmark was compared to that of the general population. Patients received powerful and prolonged treatment with phenobarbital, phenytoin, and other anticonvulsants. This new survey extends the follow-up from 1976 through 1984. Among 7,864 patients with epilepsy not known to have received radioactive Thorotrast, record linkage with national cancer incidence files identified 789 cancers, compared to 664 expected [relative risk (RR) = 1.19; 95% confidence interval = 1.11-1.27]. Significant risks were found for cancers of the brain and central nervous system (RR = 5.7; n = 118) and the lung (RR = 1.4; n = 106). The excess numbers of brain cancer were concentrated within 10 years of hospitalization (RR = 20.7; n = 80) and decreased significantly over time, which suggests that brain tumors account for the seizure disorder and are not due to phenobarbital exposure as suggested by some epidemiologic studies. No overall risk was apparent when brain cancers were excluded (RR = 1.03). Because bladder cancer was significantly decreased (RR = 0.6; n = 18), the excess risk of lung cancer may not have been related to the "anecdotal" heavy smoking reported among confined groups of epileptic patients in the early years of the study period. The incidence of malignant melanoma was also significantly low (RR = 0.5; n = 7), which suggested limited exposure to sunlight among confined patients. The risk of non-Hodgkin's lymphoma was increased, but not significantly (RR = 1.4; n = 16), which is interesting in view of previous reports suggesting an association with phenytoin. Overall, these data provide little evidence that phenobarbital and phenytoin are carcinogenic to humans, but the excess risks of lung cancer and non-Hodgkin's lymphoma among epileptic patients in our study deserve further evaluation.

Adolescent↗
PubMed1992

Cancer incidence among Danish Thorotrast-exposed patients.

BACKGROUND: Studies of groups of patients given injections of the alpha-emitting x-ray contrast medium Thorotrast may provide information on human alpha-ray carcinogenesis. PURPOSE: We re-established a formerly identified cohort of neurological patients receiving injections of Thorotrast for cerebral arteriography and assessed their incidence of cancer. METHODS: Using the national population register, the Danish Cancer Registry, and other registers, we determined the incidence of cancer among Thorotrast-injected patients. Incidence ratios were standardized to the general population and computed for different cancer sites. RESULTS: The cumulative risk for cancer at all sites (excluding brain tumors where the standardized incidence ratio [SIR] was 28) reached 86% 50 years after Thorotrast injection. SIR was greatly elevated at all sites except the brain and CNS (3.3, 95% confidence interval = 3.0-3.7), mainly because of liver cancers (SIR = 126) as well as leukemia (SIR = 10) for which a relationship was found between the time since injection and the estimated dose (but not the age at injection). Other sites with significantly increased risks of cancer included the gallbladder and extrahepatic bile ducts (SIR = 14), peritoneum (SIR = 8.6), sites of multiple myeloma (SIR = 4.6), metastatic sites (SIR = 12), and unspecified sites (SIR = 11). Cancers of the lung and breast also occurred in significant excess, but no relationship between SIR and volume of injected Thorotrast or time since injection was observed. Cancer risk was increased at most other sites, although this increase was not statistically significant. CONCLUSION: Alpha radiation may account for the increased risk of tumors of the liver, gallbladder, and peritoneum as well as leukemia and multiple myeloma, whereas confounding factors most probably contribute to the increased risks at other sites.

Adult↗
PubMed2001

Distribution of natural thorium in the tissues of a whole body.

The distribution of thorium in the tissues of a whole body donor to the United States Transuranium and Uranium Registries is described. This case, identified by the USTUR as Case 0212, had two documented intakes of plutonium and americium from occupational accidents while employed at Hanford but no known occupational exposure to thorium. Concentrations of 239+240Pu, 241Am, and 232Th in the tissues are compared and the distribution of these isotopes in this case is evaluated. The distribution data for 232Th are compared to those from previous studies of thorium in human tissues resulting from environmental exposure and to an individual exposed to Thorotrast (colloidal ThO2) in a medical diagnostic procedure. The 232Th distribution data from this work are also compared against ICRP 30 and ICRP 69 models for the behaviour of thorium in the human body.

Americium↗
PubMed2001

In vitro dissolution characteristics of aged and recrystallised high-fired 232ThO2.

The dissolution characteristics of 232Th from ThO2 in the lung have been determined in an in vitro study. Two types of ThO2 were examined to determine if the age of the material had any effect; an aged high-fired ThO2 that had its progeny in secular equilibrium, and a recently recrystallised and high-fired ThO2 in disequilibrium. The results show the amount of 232Th that dissolved from the aged ThO2 was approximately 10 times greater than the amount that dissolved from the recrystallised and fired ThO2 which was the result of recoil damage to the crystal structure of the aged material. A model based on nuclear track theory was developed to relate the size of the observed rapidly soluble fraction of 232Th to the age of the material and its experimentally determined surface area.

Crystallization↗
PubMed2006

Natural radioactivity and evaluation of effective dose equivalent of granites in Turkey.

Annual effective dose equivalent due to natural gamma radiation from (238)U, (232)Th and (40)K have been evaluated from granites in Turkey. Forty samples were taken for spectrometric analysis. Specific concentrations of (238)U, (232)Th and (40)K in granite samples were determined. Spectroscopy system was used with 1.8 keV (FWHM) coaxial high purity germanium (HPGe) detector. Average values of concentrations of (238)U, (232)Th and (40)K were detected at 15.85, 33.76 and 359 Bq kg(-1), respectively. The average value of radon varies from 0.073 to 0.185 Bq m(-2) h(-1) exhalation depends on the specific concentration of uranium. The dose rate due to this highest activity which have been evaluated by a Monte Carlo transport calculations does not exceed 0.4 mSv a(-1).

Air Pollutants, Radioactive↗
PubMed1995

Malignant peritoneal mesothelioma after Thorotrast exposure.

A case of a malignant peritoneal mesothelioma in a 63-year-old male patient with a history of exposure to Thorotrast in 1945 is presented. There was no history of exposure to asbestos. The clinical manifestation was a serosal effusion, which required weekly ascites puncture until therapy with intraperitoneal bleomycin was initiated. The latter treatment led to a significant reduction of ascites without any influence on tumor progression. Unfortunately, intraperitoneal bleomycin was accompanied by pulmonary toxicity, but at a higher total dose than known for intravenous administration. Three years after diagnosis the patient is still alive, without relapse of ascites production after bleomycin had to be stopped. Considering the risk of pulmonary fibrosis with high-dose intraperitoneal bleomycin and the lack of efficacy on tumor reduction, bleomycin seems to offer no advantage with respect to cisplatin.

Adenocarcinoma↗