| Mutations of p53 and ras genes in radon-associated lung cancer from uranium miners. | |
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MedLine Citation:
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PMID: 1347094 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Radon increases the risk of lung cancer in smoking and non-smoking underground miners. To investigate the mutational spectrum associated with exposure to high levels of radon, we sequenced exons 5-9 of the p53 tumour suppressor gene and codons 12-13 of the Ki-ras protooncogene in 19 lung cancers from uranium miners exposed to radon and tobacco smoke. Mutations were not found in Ki-ras, but 9 p53 mutations, including 2 deletions, were found in 7 patients by direct DNA sequencing after polymerase chain reaction amplification of DNA from formalin-fixed, paraffin-embedded tissue. In tumours from 5 patients, the mutation produced an aminoacid change and an increased nuclear content of p53 protein. The tumours with either a stop codon or frame-shift deletion in the p53 gene were negative by immunohistochemistry. None of the mutations were G:C to T:A transversions in the coding strand of the p53 gene, which are the most frequent base substitutions associated with tobacco smoking, and none were found at the hotspot codons described in lung cancer. The observed differences from the usual lung cancer mutational spectrum may reflect the genotoxic effects of radon. |
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Authors:
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K H Vähäkangas; J M Samet; R A Metcalf; J A Welsh; W P Bennett; D P Lane; C C Harris |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Lancet Volume: 339 ISSN: 0140-6736 ISO Abbreviation: Lancet Publication Date: 1992 Mar |
Date Detail:
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Created Date: 1992-03-31 Completed Date: 1992-03-31 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985213R Medline TA: Lancet Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 576-80 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Base Sequence Carcinoma / genetics*, pathology Chromosome Deletion Codon / genetics DNA, Neoplasm / analysis Genes, p53 / genetics* Genes, ras / genetics* Humans Lung Neoplasms / genetics*, pathology Middle Aged Mining* Molecular Sequence Data Mutation / genetics* Neoplasms, Radiation-Induced / genetics* Occupational Diseases / genetics* Polymerase Chain Reaction Radon / adverse effects* Smoking / adverse effects Uranium* |
| Grant Support | |
ID/Acronym/Agency:
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N01 CN-55426/CN/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Codon; 0/DNA, Neoplasm; 10043-92-2/Radon; 7440-61-1/Uranium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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