Skip to main content

Advertisement

SpringerLink
Log in

Discrimination of cancerous and non-cancerous cell lines by headspace-analysis with PTR-MS

  • Original Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Proton transfer reaction mass spectrometry (PTR-MS) has been used to analyze the volatile organic compounds (VOCs) emitted by in-vitro cultured human cells. For this purpose, two pairs of cancerous and non-cancerous human cell lines were selected:1. lung epithelium cells A-549 and retinal pigment epithelium cells hTERT-RPE1, cultured in different growth media; and 2. squamous lung carcinoma cells EPLC and immortalized human bronchial epithelial cells BEAS2B, cultured in identical growth medium. The VOCs in the headspace of the cell cultures were sampled: 1. online by drawing off the gas directly from the culture flask; and 2. by accumulation of the VOCs in PTFE bags connected to the flask for at least 12 h. The pure media were analyzed in the same way as the corresponding cells in order to provide a reference. Direct comparison of headspace VOCs from flasks with cells plus medium and from flasks with pure medium enabled the characterization of cell-line-specific production or consumption of VOCs. Among all identified VOCs in this respect, the most outstanding compound was m/z = 45 (acetaldehyde) revealing significant consumption by the cancerous cell lines but not by the non-cancerous cells. By applying multivariate statistical analysis using 42 selected marker VOCs, it was possible to clearly separate the cancerous and non-cancerous cell lines from each other.

The multivariate statistical analysis allowed to clearly separate the different cell lines from each other using 42 selected marker VOCs.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Thekedar B (2009) Investigations on the use of breath gas analysis with proton transfer reaction mass spectrometry (PTR-MS) for a non-invasive method of early lung cancer detection. PhD Thesis. Technical University of Munich, Munich

    Google Scholar 

  2. Bajtarevic A, Ager C, Pienz M, Klieber M, Schwarz K, Ligor M, Ligor T, Filipiak W, Denz H, Fiegl M, Hilbe W, Weiss W, Lukas P, Jamnig H, Hackl M, Haidenberger A, Buszewski B, Miekisch W, Schubert J, Amann A (2009) Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9:348

    Article  Google Scholar 

  3. Alberts B (2004) Molekularbiologie der Zelle. Weinheim, VCH Verlagsgesellschaft

    Google Scholar 

  4. Lindinger W, Hansel A, Jordan A (1998) On-line monitoring of volatile organic compounds at pptv levels by means of Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) Medical applications, food control and environmental research. Int J Mass Spectrom Ion Process 173:191–241

    Article  CAS  Google Scholar 

  5. Carroll W, Lenney W, Wang TS, Spanel P, Alcock A, Smith D (2005) Detection of volatile compounds emitted by Pseudomonas aeruginosa using selected ion flow tube mass spectrometry. Pediatr Pulmonol 39:452–456

    Article  Google Scholar 

  6. Allardyce RA, Hill AL, Murdoch DR (2006) The rapid evaluation of bacterial growth and antibiotic susceptibility in blood cultures by selected ion flow tube mass spectrometry. Diagn Microbiol Infect Dis 55:255–261

    Article  CAS  Google Scholar 

  7. Bunge M, Araghipour N, Mikoviny T, Dunkl J, Schnitzhofer R, Hansel A, Schinner F, Wisthaler A, Margesin R, Märk T (2008) On-Line Monitoring of Microbial Volatile Metabolites by Proton Transfer Reaction-Mass Spectrometry. Appl Environ Microbiol 74:2179–2186

    Article  CAS  Google Scholar 

  8. Smith D, Wang TS, Spanel P (2002) Kinetics and isotope patterns of ethanol and acetaldehyde emissions from yeast fermentations of glucose and glucose-6,6-d(2) using selected ion flow tube mass spectrometry: a case study. Rapid Commun Mass Spectrom 16:69–76

    Article  CAS  Google Scholar 

  9. Steeghs MML, Moeskops B, van Swam K, Cristescu SM, Scheepers PTJ, Harren FJM (2006) On-line monitoring of UV-induced lipid peroxidation products from human skin in vivo using proton-transfer reaction mass spectrometry. Int J Mass Spectrom 253:58–64

    Article  CAS  Google Scholar 

  10. Moeskops BWM, Steeghs MML, Kv S, Cristescu SM, Scheepers PTJ, Harren FJM (2006) Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human skin in vivo. Physiol Meas 27:1187–1196

    Article  CAS  Google Scholar 

  11. Smith D, Wang TS, Sule-Suso J, Spanel P, El Haj A (2003) Quantification of acetaldehyde released by lung cancer cells in vitro using selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom 17:845–850

    Article  CAS  Google Scholar 

  12. Kato S, Burke PJ, Koch TH, Bierbaum VM (2001) Formaldehyde in human cancer cells: Detection by preconcentration-chemical ionization mass spectrometry. Anal Chem 73:2992–2997

    Article  CAS  Google Scholar 

  13. Chen X, Xu F, Wang Y, Pan Y, Lu D, Wang P, Ying K, Chen E, Zhang W (2007) A Study of the Volatile Organic Compounds Exhaled by Lung Cancer Cells In Vitro for Breath Diagnosis. American Cancer Society 110:835–844

    CAS  Google Scholar 

  14. Filipiak W, Sponring A, Mikoviny T, Ager C, Schubert JK, Miekisch W, Amann A, Troppmair J (2008) Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-I in vitro. Cancer Cell International

  15. Bepler G, Koehler A, Kiefer P, Havemann K, Beisenherz K, Jaques G, Gropp C, Haeder M (1988) Characterization of the state of differentiation of six newly established human non-small-cell lung cancer cell lines. Differentiation 37:158–171

    Article  CAS  Google Scholar 

  16. Filipiak W, Sponring A, Filipiak A, Ager C, Schubert J, Miekisch W, Amann A, Troppmair J (2010) TD-GC–MS analysis of volatile metabolites of human lung cancer and normal cells in vitro. Cancer Epidemiol Biomark Prev 19:182–195

    Article  CAS  Google Scholar 

  17. Hansel A, Jordan A, Holzinger R, Prazeller P, Vogel W, Lindinger W (1995) Proton transfer reaction mass spectrometry: online trace gas analysis at the ppb level. Int J Mass Spectrom Ion Process 149–150:609–619

    Article  Google Scholar 

  18. Lindinger W, Hansel A, Jordan A (1998) On-line monitoring of volatile organic compounds at pptv levels by means of Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) Medical applications, food control and environmental research. Int J Mass Spectrom Ion Process 173:191–241

    Article  CAS  Google Scholar 

  19. Steinbacher A, Dommen J, Ammann C, Spirig C, Neftel A, Prevot ASH (2004) Performance characteristics of a proton-transfer-reaction mass spectrometer (PTR-MS) derived from laboratory and field measurements. Int J Mass Spectrom 239:117–128

    Article  CAS  Google Scholar 

  20. Bortz J (1999) Statistik für Sozialwissenschaftler. Springer Verlag, Berlin

    Google Scholar 

  21. Backhaus K, Erichson B, Plinke W, Weiber R (2006) Multivariante Analysemethoden. Springer Verlag, Berlin

    Google Scholar 

  22. Spanel P, Smith D (2008) Quantification of trace levels of the potential cancer biomarkers formaldehyde, acetaldehyde and propanol in breath by SIFT-MS. Journal of Breath Research 2:1–10

    Article  Google Scholar 

  23. Buhr K, van Ruth S, Delahunty C (2002) Analysis of volatile flavour compounds by Proton Transfer Reaction-Mass Spectrometry: fragmentation patterns and discrimination between isobaric and isomeric compounds. Int J Mass Spectrom 221:1–7

    Article  CAS  Google Scholar 

  24. Sponring A, Filipiak W, Mikoviny T, Ager C, Schubert JK, Miekisch W, Amann A, Troppmair J (2009) Release of Volatile Organic Compunds from the Lung Cancer Cell Line NCI-H2087 In Vitro. Anticancer Res 29:419–426

    CAS  Google Scholar 

  25. Patel M, Lu L, Zander DS, Sreerama L, Coco D, Moreb JS (2008) ALDHI AI and ALDH3 AI expression in lung cancer: correlations with histologic type and potential precursors. Lung Cancer 59:340–349

    Article  Google Scholar 

  26. Ucar D, Cogle CR, Zucali JR, Ostmark B, Scott EW, Zori R, Gray BA, Moreb JS (2009) Aldehyde dehydrogenase activity as a functional marker for lung cancer. Chem Biol Interact 178:48–55

    Article  CAS  Google Scholar 

  27. Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, Wang HM, Liu Z, Su Y, Stass SA, Katz RL (2009) Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 7:330–338

    Article  CAS  Google Scholar 

  28. Duester G (2000) Families of retinoid dehydrogenases regulating vitamin A function – Production of visual pigment and retinoic acid. Eur J Biochem 267:4315–4324

    Article  CAS  Google Scholar 

  29. Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, Takahashi N, Welch MJ, Fujibayashi Y (2001) Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells. Nucl Med Biol 28:117–122

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Klaudia Winkler and Romy Müller from the Institute of Radiation Biology of the Helmholtz Zentrum München for providing the cells, the laboratory, and the know-how for handling of in-vitro cultured cells.

Author information

Authors and Affiliations

  1. Institute of Radiology, Hospital rechts der Isar of the Technical University of Munich, 81675, Munich, Germany

    C. Brunner

  2. Helmholtz Zentrum München - German Research Center for Environmental Health, 85764, Neuherberg, Germany

    C. Brunner, W. Szymczak, V. Höllriegl, S. Mörtl, C. Hoeschen & U. Oeh

  3. Division of Respiratory Medicine, Medizinische Klink-Innenstadt, Ludwig-Maximilians-University, 80539, Munich, Germany

    H. Oelmez, A. Bergner & R. M. Huber

Authors
  1. C. Brunner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Szymczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Höllriegl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Mörtl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Oelmez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Bergner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. M. Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. Hoeschen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. U. Oeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Brunner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brunner, C., Szymczak, W., Höllriegl, V. et al. Discrimination of cancerous and non-cancerous cell lines by headspace-analysis with PTR-MS. Anal Bioanal Chem 397, 2315–2324 (2010). https://doi.org/10.1007/s00216-010-3838-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-010-3838-x

Keywords

Search

Navigation