Summary of Entire Japanese Thorotrast Follow-Up Study: Updated 1998

Mori, Takesaburo; Kido, C; Fukutomi, Kazuo; Kato, Yoshio; Hatakeyama, Shigeru; Machinami, Rikuo; Ishikawa, Yuichi; Kumatori, T.; Sasaki, Fumio; Hirota, Yutaka; Kiyosawa, K; Hayashi, Shuhei; Tanooka, Hiroshi; Sobue, Tomotaka

doi:10.2307/3580120

Cited by 38 publications

(19 citation statements)

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“…In the largest recorded long-term study of patients who had received Thorotrast, the rate ratio for all deaths of Thorotrast patients started to increase more than 20 years following Thorotrast exposure. 5 In addition, the rate ratios for liver cancer (hepatocellular carcinoma, cholangiocarcinoma and angiosarcoma), liver cirrhosis and leukemia were 35.9, 6.9 and 12.5 times higher, respectively, than for controls. 5 Our patient was exposed to Thorotrast in the 1950 s for radiographic evaluation of knee pain.…”

Section: Discussionmentioning

confidence: 90%

“…5 In addition, the rate ratios for liver cancer (hepatocellular carcinoma, cholangiocarcinoma and angiosarcoma), liver cirrhosis and leukemia were 35.9, 6.9 and 12.5 times higher, respectively, than for controls. 5 Our patient was exposed to Thorotrast in the 1950 s for radiographic evaluation of knee pain. Although the dose he received is not known, typical limb angiography involved injection of about 25 ml of Thorotrast, which contained 5 g of thorium with an activity of 0.5 mCi 232 Th and additional radioactivity from its progeny.…”

Section: Discussionmentioning

confidence: 90%

“…Interestingly, this patient did not develop liver or hematopoietic malignancies associated with Thorotrast exposure. 2,5,6,8 Histologic examination of the patient's explanted liver revealed characteristic features of long-term Thorotrast deposition. 7 With long-term exposure, the pattern of cirrhosis is often coarsely nodular.…”

Section: Discussionmentioning

confidence: 99%

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Redistribution of thorotrast into a liver allograft several years following transplantation: a case report

et al. 2004

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 90%

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Redistribution of thorotrast into a liver allograft several years following transplantation: a case report

et al. 2004

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“…Epidemiological investigations extracting disease-specific and total risk-factors associated with the use of Thorotrast have been carried on and frequently updated in several countries, with especially large cohorts in Portugal [6], Denmark [7], Sweden [8], Japan [9], Germany [10]. These studies pose the problem of the distribution of the incubation periods over a life-long time scale.…”

Section: Introductionmentioning

confidence: 99%

Thorotrast and in vivo thorium dioxide: Numerical simulation of 30 years of α radiation absorption by the tissues near a large compact source

Bianconi

2014

Physica Medica

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Background:The epidemiology of the slightly radioactive contrast agent named Thorotrast presents a very long latency period between the injection and the development of the related pathologies. It is an example of the more general problem posed by a radioactive internal contaminant whose effects are not noteworthy in the short term but become dramatic in the long period. A point that is still to be explored is fluctuations (in space and time) in the localized absorption of radiation by the tissues. Methods:A Monte Carlo simulation code has been developed to study over a 30-year period the daily absorption of α radiation by µm-sized portions of tissue placed at a distance of 0-100 µm from a model source, that approximates a compact thorium dioxide source in liver or spleen whose size is 20 µm. The biological depletion of the daughter nuclei of the thorium series is taken into account. The initial condition assumes chemically purified natural thorium. Results:Most of the absorbed dose is concentrated in a 25-µm thick layer of tissue, adjacent to the source boundary. Fluctuations where a target region with a volume of 1 µm 3 is hit by 3-5 α particles in a day or in a shorter period of time are relevant in a 1-10 µm thick layer of tissue adjacent to the source boundary, where their frequency is larger than the Poisson-law prediction.

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“…Intravascularly injected, Thorotrast remains in the reticuloendothelial system for life, and those organs are chronically irradiated by α‐particles. In particular, >60% of total Thorotrast is located in the liver 2. Several decades after injection, Thorotrast has been known to induce liver cancers, of which ICC is the most frequent type.…”

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confidence: 99%

Microsatellite instability in thorotrast‐induced human intrahepatic cholangiocarcinoma

Liu

Momoi

et al. 2002

Intl Journal of Cancer

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Thorotrast, a colloidal suspension of radioactive 232 ThO 2 that emits ␣ particles, was used as a radiographic contrast during World War II. It is known to induce liver cancers, most frequently ICC, decades after injection. Since radiation induces genomic instability, we analyzed MSI in Thorotrastinduced ICC. The frequency of MSI ؉ cases was 62.5% in Thorotrast ICC, whereas it was 22.7% in non-Thorotrast ICC. However, frameshift mutations of mononucleotide repeats were not observed in Thorotrast ICC. In addition, the MSI ؉ phenotype was not associated with the quantity of Thorotrast deposited or the latency period of ICC induction. Promoter regions of both the hMLH1 and the hMSH2 MMR genes tended to be hypermethylated in the tumor part compared to the adjacent nontumor part in Thorotrast ICC. Methylation of the hMLH1 promoter was associated with the MSI ؉ phenotype in Thorotrast ICC. In contrast, methylation status of these promoter regions was not related to MSI in nonThorotrast ICC cases. These findings suggest that MSI induced by exposure to Thorotrast mainly reflects clonal expansion of cancer cells and is partly due to inactivation of hMLH1 by hypermethylation. © 2002 Wiley-Liss, Inc. Key words: Thorotrast; microsatellite instability; cholangiocellular carcinomaIdentification of genetic changes in radiation-induced cancer can contribute to risk assessment and prevention. Thorotrast is the trade name for a 25% colloidal suspension of radioactive 232 ThO 2 that naturally emits ␣ particles (90%), ␤ particles and ␥-rays (10%). It was used as a radiographic contrast agent from the 1930s to the 1950s. 1 Intravascularly injected, Thorotrast remains in the reticuloendothelial system for life, and those organs are chronically irradiated by ␣-particles. In particular, Ͼ60% of total Thorotrast is located in the liver. 2 Several decades after injection, Thorotrast has been known to induce liver cancers, of which ICC is the most frequent type. The development of cancer is thought to be a consequence of multiple carcinogenic steps, including genetic changes such as activation of proto-oncogenes and inactivation of tumor-suppressor genes. 3 It has become evident that cancer cells exhibit a mutator phenotype. Mutator phenotype or genomic instability results from aberrations of genes that normally function in the maintenance of genetic stability.There is now considerable evidence that cells that have survived irradiation may produce descendants that manifest various biologic consequences induced by genomic instability other than irreversible damage at the time of irradiation. 4,5 A higher frequency of nonclonal chromosomal aberrations appears in clonal descendants of mouse hematopoietic stem cells more than 12 generations after ␥-irradiation. 6 A persistently increased rate of gene mutation is observed in cell populations many generations after exposure to X-rays and ␣ particles. 7 To search for genetic changes characteristic of radiation exposure, we previously analyzed p53 gene mutations in Thorotrast-laden livers. Multip...

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Summary of Entire Japanese Thorotrast Follow-Up Study: Updated 1998

Cited by 38 publications

References 2 publications

Redistribution of thorotrast into a liver allograft several years following transplantation: a case report

Redistribution of thorotrast into a liver allograft several years following transplantation: a case report

Thorotrast and in vivo thorium dioxide: Numerical simulation of 30 years of α radiation absorption by the tissues near a large compact source

Microsatellite instability in thorotrast‐induced human intrahepatic cholangiocarcinoma

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