Skip to main content

Detection of Chromosomal Aberrations in Lung Tissue and Peripheral Blood Lymphocytes Using Interphase Fluorescence In Situ Hybridization (FISH)

  • Protocol
Lung Cancer

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 75))

  • 661 Accesses

Abstract

Many cancers arise from gene-environment interactions, where susceptible individuals develop cancer after exposure to toxic or mutagenic environmental agents (1). Genetic instability, whether constitutional or induced, has long been suspected to predispose to carcinogenesis. Cytogenetic assays are classical methods for detecting genetic instability, in which chromosome aberrations are used as biomarkers of the effect of exposure to genotoxic agents. The conceptual basis of this approach revolves around the assumption that the extent of genetic damage reflects critical events in the carcinogenic process, such as an impaired ability to remove damaged DNA or failure to correctly rejoin DNA breaks (2). In a prospective study, Sorsa et al. (3) reported that subjects with a high level of chromosomal aberrations appeared to be at an elevated risk for cancer. Bonassi et al. (4) and Hagmar et al. (5), in two independent prospective studies, reported a significant increase in the mortality ratio for all cancers in subjects who had earlier shown elevated levels of chromosomal aberrations in their lymphocytes. Recently, the data from these two studies were pooled and the results indicate that the frequency of chromosome aberrations in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting early biological effects of exposure to genotoxic carcinogens and/or individual susceptibility to cancer (6,7).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hsu, T. C., Johnston, D. A., Cherry, L. M., Ramikisson, D., Schantz, S. P., Jessup, J. M., et al. (1989) Sensitivity of genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis. Int. J. Cancer 43, 403ā€“409.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  2. Heim, S. and Mitelman, F. (1987) Cancer cytogenetics. Alan R. Liss, New York, NY.

    Google ScholarĀ 

  3. Sorsa, M., Wilbourn, J., and Vainio, H. (1992) Human cytogenetic damage as a predictor of cancer risk, in Mechanisms of Carcinogenesis in Risk Identification (Vainio, H., Magee, P. N., McGregor, D. B., and McMicheal, A. J., eds.), IARC Scientific Publication No. 116. International Agency for Research on Cancer, Lyon, pp. 543ā€“554.

    Google ScholarĀ 

  4. Bonassi, S. and Abbondandolo, A. (1995) Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Cancer Genet. Cytogenet. 79, 133ā€“135.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  5. Hagmar, L., Brogger, A., Hansteen, I. L., Heim, S., Hogstedt, B., Knudsen, L., et al. (1994) Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage. Cancer Res. 54(11), 2919ā€“2922.

    PubMedĀ  CASĀ  Google ScholarĀ 

  6. Hagmar, L., Bonassi, S., Stromberg, U., Brogger, A., Knudsen, L. E., Norppa, H., et al. (1998) Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res. 58(18), 4117ā€“4121.

    PubMedĀ  CASĀ  Google ScholarĀ 

  7. Bonassi, S., Hagmar, L., Stromberg, U., Montagud, A. H., Tinnerberg, H., Forni, A., et al. (2000) Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health. Cancer Res. 60(6), 1619ā€“1625.

    PubMedĀ  CASĀ  Google ScholarĀ 

  8. Murg, M. N., Schuler, M., and Eastmond, D. A. (1999) Persistence of chromosomal alterations affecting the 1ce-q12 region in a human lymphoblastoid cell line exposed to dieposybutane and mitomycin C. Mutation Res. 446, 193ā€“203

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  9. Visakorpi, T., Hyytinen, E., Kalloiniemi, A., Isola, J., and Kalloiniemi, O. P. (1994) Sensitive detection of chromosome copy number aberrations in prostate cancer by fluorescence in situ hybridization. Am. J. Pathol. 145, 624ā€“630.

    PubMedĀ  CASĀ  Google ScholarĀ 

  10. Takahashi, S., Qian, J., Brown, J. A., Alcaraz, A., Bostwick, D. G., Liber, M. M., and Jenkins, R. B. (1994) Potential markers of prostate cancer aggressiveness detected by fluorescence in situ hybridization in needle biopsies. Cancer Res. 54, 3574ā€“3579.

    PubMedĀ  CASĀ  Google ScholarĀ 

  11. Chang, S. S. and Mar, F. F. (1997) Emerging molecular cytogenetic technologies. Cytobios. 90(360), 7ā€“22.

    PubMedĀ  CASĀ  Google ScholarĀ 

  12. Pinkel, D., Straume, T., and Gray, J. W. (1986) Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc. Natl. Acad. Sci. USA 83(9), 2934ā€“2938.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  13. Eastmond, D. A. and Pinkel, D. (1990) Detection of aneuploidy and aneuploidy-inducing agents in human lymphocytes using fluorescence in situ hybridization with chromosome-specific DNA probes. Mutat. Res. 234(5), 303ā€“318.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  14. Eastmond, D. A., Rupa, D. S., and Hasegawa, L. S. (1994) Detection of hyperdiploidy and chromosome breakage in interphase human lymphocytes following exposure to the benzene metabolite hydroquinone using multicolor fluorescence in situ hybridization with DNA probes. Mutat. Res. 32, 9ā€“20.

    Google ScholarĀ 

  15. Poddighe, P. J., Moesker, O., Smeets, D., Awwad, B. H., Ramaekers, F. C., and Hopman, A. H. (1991) Interphase cytogenetics of hematological cancer: comparison of classical karyotyping and in situ hybridization using a panel of eleven chromosome specific DNA probes. Cancer Res. 51(7), 1959ā€“1967.

    PubMedĀ  CASĀ  Google ScholarĀ 

  16. Kadam, P., Umerani, A., Srivastava, A., Masterson, M., Lampkin, B., and Raza, A. (1991) Combination of classical and interphase cytogenetics to investigate the biology of myeloid disorders: detection of masked monosomy 7 in AML. Leuk. Res. 17(4), 365ā€“374.

    ArticleĀ  Google ScholarĀ 

  17. Kibbelaar, R. E., Kok, F., Dreef, E. J., Kleiverda, J. K., Cornelisse, C. J., Raap, A. K., and Kluin, P. M. (1993) Statistical methods in interphase cytogenetics: an experimental approach. Cytometry 14(7), 716ā€“724.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  18. Abdel-Rahman, S. Z., Salama, S. A., Au, W. W., and Hamada, F. A. (2000) Role of polymorphic CYP2E1 and CYP2D6 genes in NNK-induced chromosome aberrations in cultured human lymphocytes. Pharmacogenetics 10(3), 239ā€“249.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  19. Abdel-Rahman, S. Z. and El-Zein, R. A. (2000) The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett. 159(1), 63ā€“71.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  20. El-Zein, R., Bondy, M. L., Wang, L. E., de Andrade, M., Sigurdson, A. J., Bruner, J. M., et al. (2001) Risk assessment for developing gliomas: a comparison of two cytogenetic approaches. Mutat. Res. 490(1), 35ā€“44.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  21. Obe, G. and Herha, J. (1987) Chromosomal aberrations in heavy smokers. Hum. Genet. 41, 259ā€“263.

    ArticleĀ  Google ScholarĀ 

  22. Vijayalaxmi and Evans, H. J. (1982) In vivo and in vitro effects of cigarette smoke on chromosomal damage and sister chromatid exchange in human peripheral blood lymphocytes. Mutat. Res. 92, 321ā€“332.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  23. Littlefield, L. G. and Joiner, A. A. (1986) Analysis of chromosome aberrations in lymphocytes of long-term heavy smokers. Mutat. Res. 170, 145ā€“150.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  24. Sinues, B., Izquierdo, M., and Perez, V. (1990) Chromosome aberrations and urinary thioethers in smoker. sMutat. Res. 240, 289ā€“293.

    ArticleĀ  CASĀ  Google ScholarĀ 

  25. Tawn, E. J. and Cartmell, C. L. (1989) The effect of smoking on the frequencies of asymmetrical and symmetrical chromosome exchanges in human lymphocytes. Mutat. Res. 224, 151ā€“156.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  26. van Diemen, P. C., Maasadam, D., Darroudi, F., and Natarajan, A. T. (1995) Influence of smoking habits on the frequencies of structural and numerical chromosomal aberrations in human peripheral blood lymphocytes using the fluorescence in situ hybridization (FISH) technique. Mutagenesis 10, 487ā€“495.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  27. Brinkworth, M. H., Yardley-Jones, A., Edwards, A. J., Hughes, J. A., and Anderson, D. (1992) A comparison of smokers and nonsmokers with respect to oncogene products and cytogenetic parameters. J. Occup. Med. 34, 1181ā€“1188.

    PubMedĀ  CASĀ  Google ScholarĀ 

  28. Rupa, D. S., Hasegawa, L. S., and Eastmond, D. A. (1995) Detection of chromosomal breakage in the 1cen-1q12 region of interphase human lymphocytes using multicolorfluorescence in situ hybridization with tandem DNA probes. Cancer Res. 55, 640ā€“645.

    PubMedĀ  CASĀ  Google ScholarĀ 

  29. Conforti-Froes, N., El-Zein, R., Abdel-Rahman, S. Z., Zwischenberger, J. B., and Au, W. W. (1997) Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers. Mutat. Res. 379, 53ā€“59.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  30. Larizza, L., Doneda, L., Ginelli, E., and Fossati, E. (1988) C-heterochromatin variation and transposition in tumor progression, in Cancer Metastasis: Biological and Biochemical Mechanisms and Clinical Aspects (Prodi, G., et al., eds.), Plenum Publishing Corp., New York, pp. 309ā€“318.

    Google ScholarĀ 

  31. Doneda, L., Ginelli, E., Agresti, A., and Larizza, L. (1989) In situ hybridization analysis of interstitial C-heterochromatin in marker chromosomes of two human melanomas. Cancer Res. 49, 433ā€“438.

    PubMedĀ  CASĀ  Google ScholarĀ 

  32. Smith, L. E. and Grosovsky, A. J. (1993) Genetic instability on chromosome 16 in a human B lymphoblastoid cell line. Somat. Cell. Mol. Genet. 19, 515ā€“527.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  33. Grosovsky, A. J., Parks, K., Giver, C. R., and Nelson, S. L. (1996) Clonal analysis of delayed karyotypic abnormalities and gene mutations in radiation-induced genetic instability. Mol. Cell. Biol. 16, 6252ā€“6262.

    PubMedĀ  CASĀ  Google ScholarĀ 

  34. El-Zein, R., Abdel-Rahman, S. Z., Conforti-Froes, N., Alpard, S. K., and Zwischenberger, J. B. (2000) Chromosome aberrations as a predictor of clinical outcome for smoking associated lung cancer. Cancer Lett. 158(1), 65ā€“71.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  35. Abdel-Rahman, S. Z., El-Zein, R. A., Zwischenberger, J. B., and Au, W. W. (1998) Association of the NAT1 22C7 10 genotype with increased chromosome aberrations and higher lung cancer risk in cigarette smokers. Mutat. Res. 398(1ā€“2), 43ā€“54.

    PubMedĀ  CASĀ  Google ScholarĀ 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

Ā© 2003 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

El-Zein, R.A., Abdel-Rahman, S.Z. (2003). Detection of Chromosomal Aberrations in Lung Tissue and Peripheral Blood Lymphocytes Using Interphase Fluorescence In Situ Hybridization (FISH). In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicineā„¢, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-324-0:145

Download citation

  • DOI: https://doi.org/10.1385/1-59259-324-0:145

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-920-9

  • Online ISBN: 978-1-59259-324-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics