Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro.
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 microg/cm(2)) 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.
Ruosaari
Salla T
ST
Biological Mechanisms and Prevention of Work-related Diseases, Health and Work Ability, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FI-00250 Helsinki, Finland.
Nymark
Penny E H
PE
Aavikko
Mervi M
MM
Kettunen
Eeva
E
Knuutila
Sakari
S
Hollmén
Jaakko
J
Norppa
Hannu
H
Anttila
Sisko L
SL
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics; D001194:Asbestos / Q000032:analysis / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000139:chemically induced / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D022202:Chromosomes, Artificial, Bacterial; D002888:Chromosomes, Human, Pair 19 / Q000187:drug effects*; D004781:Environmental Exposure; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D014407:Tumor Cells, Cultured
D001194:Asbestos