Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro

• Published in: Carcinogenesis (New York) 2008-05, Vol.29 (5), p.913-917
• Main Authors: Ruosaari, Salla T., Nymark, Penny E.H., Aavikko, Mervi M., Kettunen, Eeva, Knuutila, Sakari, Hollmén, Jaakko, Norppa, Hannu, Anttila, Sisko L.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemically induced; Adenocarcinoma - genetics; Asbestos; Asbestos - analysis; Asbestos - toxicity; Biological and medical sciences; Bronchi - drug effects; Bronchi - pathology; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Small Cell - chemically induced; Carcinoma, Small Cell - genetics; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - genetics; Cells, Cultured; Chromosome Aberrations - drug effects; Chromosomes, Artificial, Bacterial; Chromosomes, Human, Pair 19 - drug effects; Environmental Exposure; Epithelial Cells - drug effects; Epithelial Cells - pathology; Humans; In Situ Hybridization, Fluorescence; Lung cancer; Lung Neoplasms - chemically induced; Lung Neoplasms - genetics; Medical sciences; Nucleic Acid Hybridization; Pneumology; Tumor Cells, Cultured; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgn068

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 (MN) 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% versus 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 MN-harbouring chromosomal fragments. Furthermore, an increased frequency of rare MN containing a 19p fragment was observed after the crocidolite treatment in comparison with untreated controls (6/6000 versus 1/10 000, 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.