Carcinogenesis Advance Access published online on November 25, 2004
Carcinogenesis, doi:10.1093/carcin/bgh328
© 2004 by Oxford University Press
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1 Department of Environmental and Occupational Health and the Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15260, USA; The University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
* To whom correspondence should be addressed. 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 nonsmoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G to T transversions, in the p53 tumor suppressor gene and K-ras oncogene, suggesting 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 cyto-centrifugation, stained, and cyto-pathologically 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 thirteen (14.1%) individuals each with a p53 mutation, one (1.1%) individual with a K-ras mutation, and one (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.
Revised October 20, 2004
Accepted October 26, 2004
CANCER BIOLOGY
Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei county, China
2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA
3 Department of Environmental and Occupational Health and the Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
4 Department of Pathology, School of Medicine, Pittsburgh PA 15240, USA
5 Department of Pathology, School of Medicine, Pittsburgh PA 15240, USA; The Veterans Administration Health Care System, Pittsburgh PA 15240, USA
6 National Health and Environmental Effects Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Phouthone Keohavong, E-mail: pho1{at}pitt.edu
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