Carcinogenesis Advance Access published online on March 13, 2008
Carcinogenesis, doi:10.1093/carcin/bgn068
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Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro
1 Biological Mechanisms and Prevention of Work-related Diseases, Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland
2 Department of Information and Computer Science, Helsinki University of Technology, Espoo, Finland
3 Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
4 New Technologies and Risks, Work Environment Development, Finnish Institute of Occupational Health, Helsinki, Finland
* To whom correspondence should be addressed at: Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FI-00250 Helsinki, Finland. Tel: +358 30 474 2581; Fax: +358 30 474 2021; Email: salla.ruosaari{at}helsinki.fi
Exposure to asbestos is known to induce lung cancer, and our previous studies have suggested that specific chromosomal regions, such as 19p13, are preferentially aberrant in lung tumours of asbestos-exposed patients. Here, we further examined the association between the 19p region and exposure to asbestos, using array comparative genomic hybridization and fluorescence in situ hybridization (FISH) in lung tumours and FISH characterization of asbestos-induced micronuclei in human bronchial epithelial BEAS 2B cells in vitro. We detected an increased number of 19p losses in the tumours of asbestos-exposed patients in comparison with tumours from non-exposed subjects with similar distribution of tumour histology in both groups (13/33; 39% vs. 3/25; 12%, P=0.04). In BEAS 2B cells, a 48-h exposure to crocidolite asbestos (2.0 µg/cm2) was found to induce centromere-negative micronuclei harbouring chromosomal fragments. Furthermore, an increased frequency of rare micronuclei containing a 19p fragment was observed after the crocidolite treatment in comparison with untreated controls (6/6000 vs. 1/10000, P=0.01). The results suggest that 19p has significance in asbestos-associated carcinogenesis and that asbestos may be capable of inducing specific chromosome aberrations.
Received November 4, 2007; revised February 22, 2008; accepted February 29, 2008.
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