Carcinogenesis Advance Access originally published online on November 25, 2004
Carcinogenesis 2005 26(2):303-308; doi:10.1093/carcin/bgh328
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Carcinogenesis vol.26 no.2 © Oxford University Press 2005; all rights reserved.
ARTICLE |
Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China
1 Department of Environmental and Occupational Health and Graduate School of Public Health and 2 The University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA, 3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA, 4 Department of Pathology, School of Medicine, University of Pittsburgh and 5 Veterans Administration Health Care System, Pittsburgh, PA 15240, USA and 6 National Health and Environmental Effects Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
* To whom correspondence should be addressed: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA. Tel: +1 412 383 2087; Fax: +1 412 383 2123; Email: pho1{at}pitt.edu
Lung cancer mortality rates in the Xuan Wei County population are among the highest in China and are associated with exposure to indoor emissions from the burning of smoky coal. Previous studies of lung tumors from both non-smoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G
T transversions in the p53 tumor suppressor gene and K-ras oncogene, suggesting that these mutations were caused primarily by polycyclic aromatic hydrocarbons. In this study sputum samples from 92 individuals with no evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras mutations. Sputum cells were collected on glass slides by sputum cytocentrifugation, stained and cytopathologically analyzed. Cytologically non-malignant epithelial cells were taken from each sputum sample using a laser capture microdissection microscope and molecularly analyzed. Cells taken from the sputum of 15 (16.3%) individuals were mutation positive, including 13 (14.1%) individuals each with a p53 mutation, 1 (1.1%) individual with a K-ras mutation and 1 (1.1%) individual with a p53 and a K-ras mutation. p53 mutations were found in both the sputum of individuals with evidence of chronic bronchitis (3 of 46 or 6.5%) and those without evidence of this disease (11 of 46 or 23.9%). Therefore, mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent in non-malignant epithelial cells taken from the sputum of individuals without evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei County and were at a high risk for developing the disease.
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