BIOMAT Database Logo BIOMAT Database Logo

Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast. 1999

T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Department of Pathology, Kyoto University, Kyoto, Japan.

Thorotrast, a colloidal suspension of radioactive (232)ThO(2) that emits alpha particles, was used as a radiographic contrast agent in the 1930s-1950s. Several decades after injection, Thorotrast causes liver cancers, among which intrahepatic cholangiocarcinoma (ICC) is prominent. We investigated mutations of the RAS and the TP53 genes in archival sections of ICC induced by Thorotrast. 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. The most common mutation of the TP53 gene was A-G transitions. Interestingly, TP53 mutations were also found in noncancerous areas of livers in which Thorotrast had been deposited. Furthermore, mutations tended to accumulate in tissues from more advanced tumors. These results suggest that deposited Thorotrast continuously damages DNA in liver cells in some way, resulting in A-G transitions of the TP53 gene. However, we have not been able to rule out the possibility that genetic insults occur indirectly in the proliferating cells adjacent to the necrosis rather than being a direct effect of alpha particles.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009381 Neoplasms, Radiation-Induced Tumors, cancer or other neoplasms produced by exposure to ionizing or non-ionizing radiation. Radiation-Induced Cancer,Cancer, Radiation-Induced,Radiation-Induced Neoplasms,Cancer, Radiation Induced,Cancers, Radiation-Induced,Neoplasm, Radiation-Induced,Neoplasms, Radiation Induced,Radiation Induced Cancer,Radiation Induced Neoplasms,Radiation-Induced Cancers,Radiation-Induced Neoplasm
D011905 Genes, ras Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein. Ha-ras Genes,Ki-ras Genes,N-ras Genes,c-Ha-ras Genes,c-Ki-ras Genes,c-N-ras Genes,ras Genes,v-Ha-ras Genes,v-Ki-ras Genes,H-ras Genes,H-ras Oncogenes,Ha-ras Oncogenes,K-ras Genes,K-ras Oncogenes,Ki-ras Oncogenes,N-ras Oncogenes,c-H-ras Genes,c-H-ras Proto-Oncogenes,c-Ha-ras Proto-Oncogenes,c-K-ras Genes,c-K-ras Proto-Oncogenes,c-Ki-ras Proto-Oncogenes,c-N-ras Proto-Oncogenes,ras Oncogene,v-H-ras Genes,v-H-ras Oncogenes,v-Ha-ras Oncogenes,v-K-ras Genes,v-K-ras Oncogenes,v-Ki-ras Oncogenes,Gene, Ha-ras,Gene, Ki-ras,Gene, v-Ha-ras,Gene, v-Ki-ras,Genes, Ha-ras,Genes, Ki-ras,Genes, N-ras,Genes, v-Ha-ras,Genes, v-Ki-ras,H ras Genes,H ras Oncogenes,H-ras Gene,H-ras Oncogene,Ha ras Genes,Ha ras Oncogenes,Ha-ras Gene,Ha-ras Oncogene,K ras Genes,K ras Oncogenes,K-ras Gene,K-ras Oncogene,Ki ras Genes,Ki ras Oncogenes,Ki-ras Gene,Ki-ras Oncogene,N ras Genes,N ras Oncogenes,N-ras Gene,N-ras Oncogene,c H ras Genes,c H ras Proto Oncogenes,c Ha ras Genes,c Ha ras Proto Oncogenes,c K ras Genes,c K ras Proto Oncogenes,c Ki ras Genes,c Ki ras Proto Oncogenes,c N ras Genes,c N ras Proto Oncogenes,c-H-ras Gene,c-H-ras Proto-Oncogene,c-Ha-ras Gene,c-Ha-ras Proto-Oncogene,c-K-ras Gene,c-K-ras Proto-Oncogene,c-Ki-ras Gene,c-Ki-ras Proto-Oncogene,c-N-ras Gene,c-N-ras Proto-Oncogene,ras Gene,ras Oncogenes,v H ras Genes,v H ras Oncogenes,v Ha ras Genes,v Ha ras Oncogenes,v K ras Genes,v K ras Oncogenes,v Ki ras Genes,v Ki ras Oncogenes,v-H-ras Gene,v-H-ras Oncogene,v-Ha-ras Gene,v-Ha-ras Oncogene,v-K-ras Gene,v-K-ras Oncogene,v-Ki-ras Gene,v-Ki-ras Oncogene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D001650 Bile Duct Neoplasms Tumors or cancer of the BILE DUCTS. Bile Duct Cancer,Cancer of Bile Duct,Cancer of the Bile Duct,Neoplasms, Bile Duct,Bile Duct Cancers,Bile Duct Neoplasm,Cancer, Bile Duct,Cancers, Bile Duct,Neoplasm, Bile Duct
D001653 Bile Ducts, Intrahepatic Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct. Bile Duct, Intrahepatic,Duct, Intrahepatic Bile,Ducts, Intrahepatic Bile,Intrahepatic Bile Duct,Intrahepatic Bile Ducts
D013911 Thorium Dioxide Thorium oxide (ThO2). A radiographic contrast agent that was used in the early 1930s through about 1954. High rates of mortality have been linked to its use and it has been shown to cause liver cancer. Thorium Oxide,Thorotrast,Dioxide, Thorium,Oxide, Thorium
D016158 Genes, p53 Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53. Genes, TP53,TP53 Genes,p53 Genes,Gene, TP53,Gene, p53,TP53 Gene,p53 Gene

Related Publications

T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma.
December 2002, International journal of cancer,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Allelotypic characteristics of thorotrast-induced intrahepatic cholangiocarcinoma: comparison to liver cancers not associated with thorotrast.
February 2004, Radiation research,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Thorotrast induced cholangiocarcinoma.
September 1976, South Dakota journal of medicine,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
[Pathomorphological study of thorotrast-related intrahepatic cholangiocarcinoma--a comparison with non-thorotrast cases].
April 1986, Gan no rinsho. Japan journal of cancer clinics,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Resection of thorotrast-induced cholangiocarcinoma.
July 1983, The American journal of gastroenterology,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Thorotrast-induced cholangiocarcinoma: case report.
January 2003, Abdominal imaging,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Thorotrast induced hepatic cholangiocarcinoma and angiosarcoma.
January 1979, Human pathology,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Genetic profiling of intrahepatic cholangiocarcinoma.
May 2012, Current opinion in gastroenterology,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
[Hepatic cholangiocarcinoma in Syrian hamster induced by thorotrast administration (author's transl)].
April 1974, Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica,
T Kamikawa, and M Amenomori, and T Itoh, and H Momoi, and H Hiai, and R Machinami, and Y Ishikawa, and T Mori, and Y Shimahara, and Y Yamaoka, and M Fukumoto
Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma.
September 2021, Hepatology (Baltimore, Md.),
Copied contents to your clipboard!