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Chemical Compound Review

Thorotrast     dioxothorium

Synonyms: Thortrast, Umbrathor, Thoria, Thorianite, ThO2, ...
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Disease relevance of Thorotrast

  • Survey of thorotrast-associated liver cancers in Japan [1].
  • 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 [2].
  • A retrospective epidemiological study of deaths from hepatic angiosarcoma (HAS) in the U.S. showed that during 1964--74 there were 168 such cases, of which 37 (22%) were associated with previously known causes (vinyl chloride, 'Thorotrast', and inorganic arsenic) and 4 (3.1%) of the remaining 131 cases with the use of androgenic-anabolic steroids [3].
  • Our results suggest that the increased risk for cancers of the liver and biliary tract among Danish epileptic patients is likely to be due to Thorotrast administration and factors associated with cirrhosis of the liver rather than to anticonvulsive treatment [4].
  • A human hepatoma cell line, associated with thorotrast exposure, from an hepatitis B marker-negative patient was established as a permanent cell line (Mz-Hep-1) in tissue culture [5].

Psychiatry related information on Thorotrast


High impact information on Thorotrast

  • 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] [7].
  • When yearly distribution, age, and time after thorotrast injection of patients with HPC were correlated with those of patients with other liver cancers, the only statistically significant difference between patients with HPC and patients with CLC (P less than 0.02) was in the years after thorotrast administration [1].
  • The lack of fusion was evident in both fluorescence and electron micrographic studies which followed the transfer of acridine orange or Thorotrast from 2 degrees lysosomes to phagosomes [8].
  • Experiments with cationized ferritin and Thorotrast provide evidence that internalization of these macromolecules takes place through the pits by pinocytosis [9].
  • By the use of Thorotrast, we were able to demonstrate that the cell surface is deeply infolded, extending all the way to the hip joint [10].

Chemical compound and disease context of Thorotrast


Biological context of Thorotrast


Anatomical context of Thorotrast

  • Intravenously administered Thorotrast was observed in endothelial cells and in the extravascular spaces within 3 min after injection into thrombocytopenic animals, while it was seen only intravascularly in control rabbits [17].
  • Use of electron-dense thoria particles to mark donor cells demonstrated the presence of injected cytoplasm in the vacuoles [18].
  • In previous studies, this structure has often been described merely as "fibrin". After i.v. injection of Thorotrast, sterile vegetations showed remarkable accumulations of mononuclear phagocytes containing this substance, on surfaces projecting into the bloodstream [19].
  • Minimal Thorotrast deposition in parapancreatic lymph nodes [20].
  • The evidence from Thorotrast transfer and assessment of yeast viability indicates that C. albicans largely resists intracellular killing by resident macrophages in the face of entirely uninhibited P-LF [21].

Associations of Thorotrast with other chemical compounds


Gene context of Thorotrast

  • We investigated mutations of the RAS and the TP53 genes in archival sections of ICC induced by Thorotrast [25].
  • Compared to ICC that was not associated with Thorotrast, the frequency of mutation of the KRAS gene was lower, while that of the TP53 gene was more than two times higher [25].
  • Methylation of the hMLH1 promoter was associated with the MSI(+) phenotype in Thorotrast ICC [6].
  • 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 [6].
  • The CAA-->CTA mutation, previously found at codon 61 of the Ha-ras gene in rat HCC, was observed in 5 further VC-induced HCC but was not detected in the Thorotrast-induced HCC, suggesting carcinogen-specificity [26].

Analytical, diagnostic and therapeutic context of Thorotrast


  1. Survey of thorotrast-associated liver cancers in Japan. Yamada, S., Hosoda, S., Tateno, H., Kido, C., Takahashi, S. J. Natl. Cancer Inst. (1983) [Pubmed]
  2. Cancer incidence among Danish Thorotrast-exposed patients. Andersson, M., Storm, H.H. J. Natl. Cancer Inst. (1992) [Pubmed]
  3. Hepatic angiosarcoma associated with androgenic-anabolic steroids. Falk, H., Thomas, L.B., Popper, H., Ishak, K.G. Lancet (1979) [Pubmed]
  4. Antiepileptic treatment and risk for hepatobiliary cancer and malignant lymphoma. Olsen, J.H., Schulgen, G., Boice, J.D., Whysner, J., Travis, L.B., Williams, G.M., Johnson, F.B., McGee, J.O. Cancer Res. (1995) [Pubmed]
  5. Hepatocellular carcinoma after thorotrast exposure: establishment of a new cell line (Mz-Hep-1). Dippold, W.G., Dienes, H.P., Knuth, A., Sachsse, W., Prellwitz, W., Bitter-Suermann, D., Meyer zum Büschenfelde, K.H. Hepatology (1985) [Pubmed]
  6. Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma. Liu, D., Momoi, H., Li, L., Ishikawa, Y., Fukumoto, M. Int. J. Cancer (2002) [Pubmed]
  7. Cancer among epileptic patients exposed to anticonvulsant drugs. Olsen, J.H., Boice, J.D., Jensen, J.P., Fraumeni, J.F. J. Natl. Cancer Inst. (1989) [Pubmed]
  8. Intralysosomal accumulation of polyanions. I. Fusion of pinocytic and phagocytic vacuoles with secondary lysosomes. Kielian, M.C., Steinman, R.M., Cohn, Z.A. J. Cell Biol. (1982) [Pubmed]
  9. Internalization of macromolecules from the medium in Suctoria. Rudzinska, M.A. J. Cell Biol. (1980) [Pubmed]
  10. Movement generated by interactions between the dense material at the ends of microtubles and non-actin-containing microfilaments in Sticholonche zanclea. Cachon, J., Cachon, M., Tilney, L.G., Tilney, M.S. J. Cell Biol. (1977) [Pubmed]
  11. Ghost infantile vertebrae and hemipelves within adult skeleton from thorotrast administration in childhood. Teplick, J.G., Head, G.L., Kricun, M.E., Haskin, M.E. Radiology. (1978) [Pubmed]
  12. Mutations in the tumor suppressor gene p53 in human liver cancer induced by alpha-particles. Andersson, M., Jönsson, M., Nielsen, L.L., Vyberg, M., Visfeldt, J., Storm, H.H., Wallin, H. Cancer Epidemiol. Biomarkers Prev. (1995) [Pubmed]
  13. Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation. Harrison, J.D., Muirhead, C.R. Int. J. Radiat. Biol. (2003) [Pubmed]
  14. Endothelial cell origin of thorium oxide-induced angiosarcoma of liver. Manning, J.T., Ordonez, N.G., Barton, J.H. Arch. Pathol. Lab. Med. (1983) [Pubmed]
  15. p53 mutations in tumor and non-tumor tissues of thorotrast recipients: a model for cellular selection during radiation carcinogenesis in the liver. Iwamoto, K.S., Fujii, S., Kurata, A., Suzuki, M., Hayashi, T., Ohtsuki, Y., Okada, Y., Narita, M., Takahashi, M., Hosobe, S., Doishita, K., Manabe, T., Hata, S., Murakami, I., Hata, S., Itoyama, S., Akatsuka, S., Ohara, N., Iwasaki, K., Akabane, H., Fujihara, M., Seyama, T., Mori, T. Carcinogenesis (1999) [Pubmed]
  16. Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status. Andersson, M., Wallin, H., Jönsson, M., Nielsen, L.L., Visfeldt, J., Vyberg, M., Bennett, W.P., De Benedetti, V.M., Travis, L.B., Storm, H.H. Int. J. Cancer (1995) [Pubmed]
  17. Ultrastructural changes of endothelium associated with thrombocytopenia. Kitchens, C.S., Weiss, L. Blood (1975) [Pubmed]
  18. Structural responses of amoebae to the injection of heterologous cytoplasm. Flickinger, C.J., Read, G.A., Kabana, E.M. J. Cell. Sci. (1980) [Pubmed]
  19. Experimental bacterial endocarditis. IV. Structure and evolution of very early lesions. Durack, D.T. J. Pathol. (1975) [Pubmed]
  20. Minimal Thorotrast deposition in parapancreatic lymph nodes. Okuda, K., Ichinohe, A., Kono, K., Ueda, S., Noguchi, T. Radiology. (1976) [Pubmed]
  21. Discrepancy in assessment of phagosome-lysosome fusion with two lysosomal markers in murine macrophages infected with Candida albicans. Mor, N., Goren, M.B. Infect. Immun. (1987) [Pubmed]
  22. Intrahepatic cholangiocarcinoma: radiologic-pathologic correlation. Ros, P.R., Buck, J.L., Goodman, Z.D., Ros, A.M., Olmsted, W.W. Radiology. (1988) [Pubmed]
  23. Effect of glucocorticosteroids on phagosome-lysosome interaction. Furth, R.V., Jones, T.C. Infect. Immun. (1975) [Pubmed]
  24. Thorotrast-associated gliosarcoma. Including comments on thorotrast use and review of sequelae with particular reference to lesions of the central nervous system. Wargotz, E.S., Sidawy, M.K., Jannotta, F.S. Cancer (1988) [Pubmed]
  25. Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast. Kamikawa, T., Amenomori, M., Itoh, T., Momoi, H., Hiai, H., Machinami, R., Ishikawa, Y., Mori, T., Shimahara, Y., Yamaoka, Y., Fukumoto, M. Radiat. Res. (1999) [Pubmed]
  26. Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species. Boivin-Angèle, S., Lefrançois, L., Froment, O., Spiethoff, A., Bogdanffy, M.S., Wegener, K., Wesch, H., Barbin, A., Bancel, B., Trépo, C., Bartsch, H., Swenberg, J., Marion, M.J. Int. J. Cancer (2000) [Pubmed]
  27. Cutaneous Thorotrast granulomas and chronic lymphocytic leukemia following Thorotrast angiography. Wargotz, E.S. Am. J. Surg. Pathol. (1985) [Pubmed]
  28. Thorotrast induced adhesive arachnoiditis associated with meningioma and schwannoma. Meyer, M.W., Powell, H.C., Wagner, M., Niwayama, G. Hum. Pathol. (1978) [Pubmed]
  29. Redistribution of thorotrast into a liver allograft several years following transplantation: a case report. Krasinskas, A.M., Minda, J., Saul, S.H., Shaked, A., Furth, E.E. Mod. Pathol. (2004) [Pubmed]
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