Abstract
Four primary cancers found at autopsy of a patient who received the thorium-based contrast agent Thorotrast 50 years ago and who was healthy up until a few months before his death from liver failure were analyzed for p53 mutations. The data suggest that the chronic alpha-irradiation may be a large causative factor. Multiple mutations were found in all the cancer tissues: two foci of a cholangiocellular carcinoma, a tubular adenocarcinoma of the stomach, a squamous cell carcinoma of the lung, and an adenocarcinoma of Vater's ampulla. The total number of point mutations detected were 13. Moreover, homozygous aberrations were detected in a large area of normal small intestine and noncancer liver tissues suggesting that nontumor cells which harbored p53 abnormalities gained a survival advantage and clonally expanded.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology
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Aged
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Alleles
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Ampulla of Vater / pathology
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / pathology
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Cholangiocarcinoma / genetics
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Cholangiocarcinoma / pathology
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Common Bile Duct Neoplasms / genetics
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Common Bile Duct Neoplasms / pathology
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DNA, Neoplasm / analysis
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Fatal Outcome
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Genes, p53 / genetics*
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Humans
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology
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Lung Neoplasms / genetics
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Lung Neoplasms / pathology
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Male
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Neoplasms, Multiple Primary / chemically induced
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Neoplasms, Multiple Primary / genetics*
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Neoplasms, Multiple Primary / pathology
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Point Mutation
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Polymerase Chain Reaction
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Polymorphism, Restriction Fragment Length
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Stomach Neoplasms / genetics
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Stomach Neoplasms / pathology
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Thorium Dioxide / adverse effects*
Substances
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DNA, Neoplasm
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Thorium Dioxide