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

Our plain-English summary of Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro, by S.T. Ruosaari, P.E. Nymark, M.M. Aavikko, et al (Carcinogenesis, 2008).

The study

• Authors: S.T. Ruosaari, P.E. Nymark, M.M. Aavikko, E. Kettunen, S. Knuutila, J. Hollmén, H. Norppa, S.L. Anttila
• Journal: Carcinogenesis
• Published: 2008;29(5):913-7
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This laboratory study asked whether the short arm of chromosome 19 (19p) is damaged more often in lung cancers of asbestos-exposed Finnish patients. Patients counted as exposed if they had worked with asbestos and had more than 1 million asbestos fibres per gram of dry lung. A genetic staining test (FISH) on 58 tumours found 19p losses in 39% (13/33) of exposed and 12% (3/25) of non-exposed patients' tumours (P = 0.04). A finer genome analysis of 10 tumours, pooled with earlier data on 16 more, showed similar differences, but they were not statistically significant. Separately, laboratory-grown human airway cells were treated with crocidolite for 48 hours. Crocidolite raised the rate of cells holding small extra nuclei (micronuclei) made of chromosome fragments 1.7 times over untreated cells. Cells with micronuclei containing a 19p piece were 10 times more frequent: 6 of 6000 treated cells versus 1 of 10 000 untreated cells (P = 0.01). The authors concluded that their results suggest asbestos exposure plays a part in chromosome 19 damage, especially 19p losses, and that further studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study combining genetic analysis of human lung tumour samples (array comparative genomic hybridization and fluorescence in situ hybridization, FISH) with an in vitro experiment exposing human bronchial epithelial cells to crocidolite
• Who was studied: Lung tumours from Finnish lung cancer patients. Fine-resolution oligonucleotide array CGH was done on 10 tumours (5 exposed, 5 non-exposed). These were combined with earlier complementary DNA microarray data on 16 more tumours (7 exposed, 9 non-exposed), giving 26 tumours in total (12 exposed, 14 non-exposed). FISH was done on 58 tumours: 33 exposed (32 men and 1 woman) and 25 non-exposed (all men). The lab experiment used immortalized human bronchial epithelial BEAS 2B cells. Dates of patient collection are not given.
• Exposure: In patients, exposed meant a history of occupational asbestos exposure plus a lung fibre concentration above 1 million fibres per gram of dry lung tissue. Non-exposed meant no exposure history and fewer than 0.5 million fibres per gram. In the FISH group, the median fibre count was 9.3 (range 1.3 to 184) million per gram in exposed patients and 0.0 (range 0.0 to 0.5) in non-exposed patients. The fibre type in patients' lungs is not specified. In the cell experiment, the exposure was crocidolite at 2.0 micrograms per square centimetre for 48 hours, with mitomycin C as a positive control and untreated cells as a negative control.
• Main results:
  • By FISH, losses of 19p were found in 39% (13/33) of tumours from exposed patients and 12% (3/25) of tumours from non-exposed patients (P = 0.04, Fisher's exact test).
  • By FISH, gains of 19p were more common in non-exposed than exposed patients' tumours (text: 36%, 9/25, versus 18%, 6/33). The difference was not statistically significant.
  • The authors combined the 10 oligonucleotide array CGH tumours with earlier complementary DNA microarray data on 16 more. In this combined data, loss of 19p or of chromosome 19 was found in 42% (5/12) of exposed and 14% (2/14) of non-exposed patients' tumours. A break at the centromeric region was found in 67% (8/12) versus 36% (5/14). These differences were not statistically significant.
  • In BEAS 2B cells, crocidolite increased the frequency of binucleate cells with centromere-negative micronuclei (those holding chromosome fragments) 1.7-fold compared with untreated controls (P = 0.008). Mitomycin C caused a 4.8-fold increase.
  • Among centromere-negative micronuclei, a 19p fragment was found in 3.4% (6/176) after crocidolite, 1.4% (2/139) after mitomycin C and 0.6% (1/159) in untreated controls. The crocidolite-versus-control difference was not quite statistically significant (P = 0.079).
  • Measured against total cells scored, cells with micronuclei holding a 19p fragment were 10 times more frequent in crocidolite-treated cultures (6 of 6000 cells scored) than in untreated controls (1 of 10 000 cells scored), P = 0.01.
  • In crocidolite-treated cells, the observed 3.4% share of 19p fragments was 3.6 times the value expected if breakage were random (0.945%). This difference was not statistically significant.
• The authors' conclusion: The authors concluded that their studies suggest asbestos exposure has importance in causing aberrations of chromosome 19, especially losses of 19p. They added that further studies are needed to confirm the relevance of 19p in lung carcinogenesis.
• Limitations the authors state:
  • Because few samples were analyzed, thorough comparisons between tumour types (for example small cell versus large cell carcinoma) were not possible.
  • The frequency of cells that had lost 19p to micronuclei after the 48-hour crocidolite treatment was rather low (1/1000 cells).
  • The authors state that further studies are needed to confirm the relevance of 19p and other suspected asbestos-related hot spots in lung carcinogenesis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Micronuclei, Fluorescence In Situ Hybridization (FISH), Histology, Crocidolite, Carcinogenesis.

Related studies

• Karyotype analysis of tumorigenic human bronchial epithelial cells transformed by chrysolite asbestos using chemically induced premature chromosome condensation technique — M. Suzuki, C.Q. Piao, et al. (2001)
• Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers — E. Dopp, M. Schuler, et al. (1997)
• Metsovo-tremolite asbestos fibres: in vitro effects on mutation, chromosome aberration, cell transformation and intercellular communication — K. Athanasiou, S.H. Constantopoulos, et al. (1992)
• DNA damage in bronchial epithelial and mesothelial cells with and without associated crocidolite asbestos fibers — J. Nygren, S. Suhonen, et al. (2004)
• Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro — A. Iakhiaev, U. Pendurthi, et al. (2004)
• Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway — M. Zhang, J. Chen, et al. (2017)

Browse more research in Carcinogenesis, or return to medical research.