Skip to main content
SpringerLink
Log in

The Analysis of Drug-Induced Cell Cycle Perturbations by Flow Cytometry

  • Chapter
Analytical Use of Fluorescent Probes in Oncology

Part of the book series: NATO ASI Series ((NSSA,volume 286))

  • 134 Accesses

Abstract

The understanding of cell cycle kinetics in both normal and malignant cells is becoming increasingly important for both the laboratory scientist and the clinician. Techniques of flow cytometry, which have developed in the last 30 years, have allowed for the rapid assessment of the cell cycle kinetics of large numbers of individual cells. These techniques can provide information on cell volume, DNA and protein content as well as more sophisticated measures of biochemical activity. The obvious application to oncology is the ability to begin to explore the genetic differences between normal and malignant cells. Transformation of normal cells to malignant cells involves changes in cellular DNA and kinetics. With flow cytometry, one can exploit these changes in order to study tumor behavior.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. van Dilla MA, Trujillo TT, Mullaney PR Cell microfluorometry: Its method for rapid fluorescence measurement. Science 163, 1213–1218 (1969)

    Article  PubMed  Google Scholar 

  2. Fulwyler MJ. Electronic separation of biological cells by volume. Science 150, 910–913 (1965)

    Article  PubMed  CAS  Google Scholar 

  3. Kamentsky LA and Melamed MR. Spectrophotometric cell sorter. Science 156, 1364–1367 (1967).

    Article  PubMed  CAS  Google Scholar 

  4. Crissman HA and Steinkamp JA Multivariate Cell Analysis: Techniques for correlated measurements of DNA and other cellular constituents, in Techniques in Cell Cycle Analysis (JW Gray and Z Darzynkiewicz, Eds.) Humana Press, Clifton, NJ, pp. 163–206 (1987).

    Chapter  Google Scholar 

  5. LePecq JB and Paoletti C. A new fluorometric method for RNA and DNA determination. Anal Biochem 17, 100(1966).

    Google Scholar 

  6. Krishnan A. Rapid flow cytometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol 66, 188(1937).

    Google Scholar 

  7. Traganos F, Darzynkiewicz Z, Sharpless R. Simultaneous staining of ribonucleic and deoxyribonucleic acid in unfixed cells using acridine orange in a flow cytometric system J Histochem Cytochem 25, 46 (1977).

    Article  PubMed  CAS  Google Scholar 

  8. Roti Roti JL, Higashikubo R, Blair OC, Uygur N. Cell-cycle position and nuclear protein content. Cytometry 3, 91–96 (1982).

    Article  Google Scholar 

  9. Pollack, A., Moulis, H., Block, N., and Irvin, G. Quantitation of cell kinetic responses using simultaneous flow cytometric measurements of DNA and nuclear protein, Cytometry 5, 473–481 (1984).

    Article  PubMed  CAS  Google Scholar 

  10. Gerner EW and Humphrey RM. The cell-cycle phase synthesis of non-histone proteins in mammalian cells. Biochem Biophys Acta 331, 117–123 (1973).

    Article  PubMed  CAS  Google Scholar 

  11. Averette HE, Weinstein GD, Frost P. Autoradiographic analysis of cell proliferation kinetics in human genital tissues. I. Normal cervix and vagina, Am J Obst Gynecol 108, 8–17 (1970).

    CAS  Google Scholar 

  12. Averette HE, Weinstein GD, Ford JH, Hoskins WJ, Ramos R. Cell kinetics and programmed chemotherapy for gynecologic cancer, I. Squamous cell carcinoma, Am J Obst Gynecol 12, 912–923 (1976).

    Google Scholar 

  13. Yataganas X and Clarkson BD. Flow microfluorometric analysis of cell killing with cytotoxic drugs. J Histochem Cytochem 22, 651–659 (1974).

    Article  PubMed  CAS  Google Scholar 

  14. Sorenson, C. and Eastman, A. Mechanism of cis-diaminedichloroplatinum-induced cytotoxicity: Role of G2 arrest and DNA double-strand breaks, Cancer Res. 48, 4484–4488 (1988).

    PubMed  CAS  Google Scholar 

  15. Sorenson, C, Barry, M., and Eastman, A. Analysis of events associated with cell cycle arrest at G2 phase and cell death induced by cisplatin, J Natl Cancer Inst 82, 749–755 (1990).

    Article  PubMed  CAS  Google Scholar 

  16. Ormerod, M., Orr, R., and Peacock, J. The role of apoptosis in cell killing by cisplatin: A flow cytometric study, Br J Cancer 69, 93–100 (1994).

    Article  PubMed  CAS  Google Scholar 

  17. Barlogie, B., Drewinko, B., Schumann, J., and Greireich, E. Pulse cytophotometric analysis of cell cycle perturbation with bleomycin in vitro, Cancer Res 36, 1182–1187 (1976).

    PubMed  CAS  Google Scholar 

  18. Engelholm, S.A., Spang-Thomsen, M., and Vindelov, L.L. A short-term in vitro test for tumour sensitivity to adriamycin based on flow cytometric DNA analysis, Br J Cancer 47, 497–502 (1983).

    Article  PubMed  CAS  Google Scholar 

  19. Hamburger, A.W., and Salmon, S.G. Primary bioassay of human tumor stem cells, Science 197, 461 (1977).

    Article  PubMed  CAS  Google Scholar 

  20. Engelholm, S., Spang-Thomsen, M., Vindelov, L., and Brunner, N. Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro, Cytometry 7, 243–250 (1986).

    Article  PubMed  CAS  Google Scholar 

  21. Schabel, F.M. Use of tumor growth kinetics in planning “curative” chemotherapy in advanced solid tumors, Cancer Res 29, 2384–2389 (1969).

    PubMed  Google Scholar 

  22. Kuo, S., and Luh, K. Monitoring tumor cell kinetics in patients receiving chemotherapy for small cell lung cancer, Acta Cytol 37, 353–357 (1993).

    PubMed  CAS  Google Scholar 

  23. Bergerat, J.P., and Barbologie, B. In vitro cytokinetic response of colon cancer cells to cisdichlorodiam-mineplatinum, Cancer Res 39, 4356–4363 (1979).

    Google Scholar 

  24. Latt, S.A. Microfluorometric detection of deoxyribonucleic acid replication in human metaphase chromosomes, Proc Natl Acad Sci USA 70, 3395–3399 (1973).

    Article  PubMed  CAS  Google Scholar 

  25. Dolbeare, F., Gratzner, H.G., Pallavicini, M.G., and Gray, J.W. Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine, Pr oc Natl Acad Sci USA 80, 5573–5577 (1983).

    Article  CAS  Google Scholar 

  26. Demarcq, C., Bastian, G., and Remvikos, Y. BrdUrd/DNA flow cytometry analysis demonstrates cis-diamminedichloroplatinum-induced multiple cell-cycle modifications on human lung carcinoma cells, Cytometry 13, 416–422 (1992).

    Article  PubMed  CAS  Google Scholar 

  27. Fujikane, T. Flow cytometric analysis of the kinetic effects of cisdiamminedichloroplatinum on lung cancer cells, Cytometry 10, 788–795 (1989).

    Article  PubMed  CAS  Google Scholar 

  28. Briffod. M., Spyratos, F., Hacene, K., Tubiana-Hulin, M., Pallud, C., Gilles, F., and Rouesse, J., Evaluation of breast carcinoma chemosensitivity by flow cytometric DNA analysis and computer assisted image analysis, Cytometry 13, 250–258 (1992).

    Article  PubMed  CAS  Google Scholar 

  29. Remvikos, Y., Jouve, M, Beuzeboc, P., Viehl, P., Magdelenat, H., and Pouillart, P. Cell cycle modifications of breast cancers during neoadjuvant chemotherapy: A flow cytometry study on fine needle aspirates, Eur JCancer 29, 1843–1848(1993).

    Google Scholar 

  30. Spyratos, F., Briffod, M., Tubiana-Hulin, M, Andrieu, C, Mayras, C, Pallud, C, Lasry, S., and Rouesse, J. Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma, Cancer 69, 470–475(1992).

    Google Scholar 

  31. Sevin, B.-U., Pollack, A., Averette, H., Ramos, R., Greening, S., and Evans, D. In vivo chemosensitivity testing in patients with gynecologic malignancies and nude mouse xenografts by monitoring cell kinetic parameters and DNA distribution patterns: A preliminary report, Gynecol Oncol 24, 27–40 (1986).

    Article  PubMed  CAS  Google Scholar 

  32. Sevin, B.-U., Pollack, A., Averette, H., Ramos, R., and Donato, D In vivo cell kinetic effects of cis-platinum on human ovarian cancer xenografts measured by dual parameter flow cytometry, Cytometry 8, 153–162(1987).

    Google Scholar 

  33. Nguyen, H., Sevin, B.-U., Averette, H., Perras, J., Ramos, R., Donato, D., Ochiai, K., and Penalver, M. Cell cycle perturbations of platinum derivatives on two ovarian cancer cell lines, Cancer Invest 11, 264–275(1993).

    Google Scholar 

  34. Byfield, L.E., Murnine, J., Ward, J.F., Calabro-Jones, P., Lynch, M, and Kulhnian, F. Mice, men, mustards, and methylated xanthines: The role of caffeine and related drugs in the sensitization of human tumours to alkylating agents, Br J Cancer 43, 669–683 (1981).

    Article  PubMed  CAS  Google Scholar 

  35. Lau, C.C, and Pardee, A. Mechanisms by which caffeine potentiates lethality of nitrogen mustard, Proc Natl Acad Sci 79, 2942–2946 (1982).

    Article  PubMed  CAS  Google Scholar 

  36. Schiano, M., Sevin B.-U., Perras, J., Ramos, R., Wolloch, E., and Averette, H. In vitro enhancement of cis-platinum antitumor activity by caffeine and pentoxifylline in a human ovarian cell line, Gynecol Oncol 43, 37–45(1991).

    Google Scholar 

  37. Perras, J.P., Ramos, R., and Sevin, B.-U. Demonstration of an S phase population of cells without DNA synthesis generated by displatin and pentoxifylline, Cytometry 14, 441–448 (1993).

    Article  PubMed  CAS  Google Scholar 

  38. Nguyen, H.N., Sevin, B.-U., Averette, H.E., and Perras, J.P. In vitro evaluation of a novel chemotherapeutic agent, Adozelesin, in gynecologic cancer cell lines. Cancer Chemother Pharmacol 30(1), 37–42 (1992).

    Article  PubMed  CAS  Google Scholar 

  39. Nguyen, H.N., Sevin, B.-U., Averette, H.E., Perras, J.P., Untch, M., Ramos, R., Donato, D., and Penalver, M. Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines, Gynecol Oncol 45(2), 164–173(1992).

    Article  PubMed  Google Scholar 

  40. Petru, E., Sevin, B.-U., Haas, J., Ramos, R., and Perras, J. A correlation of cell cycle perturbations with chemosensitivity in human ovarian cancer cells exposed to cytotoxic drugs in vitro, Gynecol Oncol 58, 48–57(1995).

    Google Scholar 

  41. Gibbons, W.E., Battin, D.A., and diZerega, G.S. Mechanisms of action of reproductive hormones, in Infertility, Contraception and Reproductive Endocrinology (D.R. Mishell, Jr. and Val Davajan, Eds.) Medical Economics Book, New Jersey, pp.31–44(1986).

    Google Scholar 

  42. Nguyen, H.N., Sevin, B.-U., Averette, H.E., Perras, J., Ramos, R., Penalver, M., and Donato, D. The effects of pro vera On chemotherapy of uterine cancer cell lines, Gynecol Oncol 42, 165–177 (1991).

    Article  PubMed  CAS  Google Scholar 

  43. Nguyen, H.N., Sevin, B.-U., Averette, H.E., Gottlieb, C.F., Perras, J., Ramos, R., Donato, D., and Penalver, M. The use of ATP bioluminescence assay and flow cytometry in predicting radiosensitivity of uterine cancer cell lines: Correlation of radiotoxicity and cell cycle kinetics, Gynecol Oncol 46, 88–96 (1992).

    Article  PubMed  CAS  Google Scholar 

  44. Wolloch, E., Sevin, B.-U., Perras, J., Gottlieb, C, Pollack, A., Ramos, R., Schiano, M., and Averette, H. Cell kinetic perturbations after irradiation and caffeine in the BG-1 ovarian cancer cell line, Gynecol Oncol 43, 29–36 (1991).

    Article  PubMed  CAS  Google Scholar 

  45. Schiff, P.B., Fant, J., and Horowitz, S.B. Promotion of microtubule assembly in vitro by taxol, Nature 22, 665–667(1986).

    Google Scholar 

  46. Steren, A., Sevin, B.-U., Perras, J., Ramos, R., Angioli, R., Nguyen, H., Kochli, O., and Averette, H. Taxol as a radiation sensitizer: A flow cytometric study, Gynecol Oncol 50, 89–93 (1993).

    Article  PubMed  CAS  Google Scholar 

  47. Friedlander, M.L., Hedley, D.W., Taylor, J.W., Rüssel, P., Coates, A.S., Tattersal, M.H.N., Influence of cellular DNA index on survival in advanced ovarian cancer, Cancer Res 44, 397–400 (1984).

    PubMed  CAS  Google Scholar 

  48. Erba, E., Vaghi, M., Pepe, S., Amato, G., Bistoelfi, M., Ubezio, P, Mangioni, C, Landoni, E, and Morasca, L. DNA index of ovarian carcinomas in 56 patients: In vivo and in vitro studies, Br J Cancer 52, 564–573 (1985).

    Article  Google Scholar 

  49. Iverson, O.E., Skaarland, E. Ploidy assessment of benign and malignant ovarian tumors by flow cytometry, a clinicopathologic study, Cancer 60, 82–87 (1987).

    Article  Google Scholar 

  50. Rodenburg, C.J., Cornelisse, C.H., Heintz, P.A.M., Hermans, J., Fleuren, G.T. Tumor ploidy as a major prognostic factor in advanced ovarian cancer, Cancer 59, 317–323 (1987).

    Article  PubMed  CAS  Google Scholar 

  51. Kallionemi, O.P., Punnonem, R., Martilla, J., Lehtinen, M., and Koivulla, T. Prognostic significance of DNA index, multiploidy, and S-phase fraction in ovarian cancer. Cancer 61, 334–339 (1988).

    Article  Google Scholar 

  52. Zanetta, G., Keeney, G., Cha, S., Wieand, H.S., Katzmann, J., Padratz, K.C., and Farr, G. The prognostic significance on long-term survival of flow cytometric DNA measurement in advanced ovarian cancer (abstr), Proceedings of ASCO 14, 274 (1995).

    Google Scholar 

  53. Jacobsen, A. Prognostic impact of ploidy level in carcinoma of the cervix, Am J Clin Oncol 7, 475–480 (1984).

    Article  Google Scholar 

  54. Moberger, B., Auer, G., Forslund, G., and Moberger, G. The prognostic significance of DNA measurements in endometrial carcinoma, Cytometry 5, 430–436 (1984).

    Article  PubMed  CAS  Google Scholar 

  55. Tribukait, B., Gustafson, H., and Esposti, PL. The significance of ploidy and proliferation in the clinical and biologic evaluation of bladder tumors: A study of 100 untreated cases, Br J Urol 54, 130–135(1982).

    Google Scholar 

  56. Tribukait, B., Ronstrom, L., and Esposti, P. Quantitative and qualitative aspects of flow DNA measurements related to the cytologic grade in prostatic carcinoma, Anal Quant Cytol 5, 107–111 (1983).

    PubMed  CAS  Google Scholar 

  57. Frankfurt, O.S., Arbuck, S.G., Chin, J.L., Greco, W.R., Pavelic, Z.P., Slocum, H.K., Mittelman, A., Piver, S.R., Pontes, E.J., and Rustum, Y.M. Prognostic applications of DNA flow Cytometry for hman solid tumors, in Clincical Cytometry: Annals of the New York Academy of Sciences, vol. 468 (M. Andreeff, Ed.), New York,NY, pp. 276–290 (1986).

    Google Scholar 

  58. Meyer, J.S., and Prioleau, P.G. S phase fractions of colorectal carcinomas related to pathological and clinical features, Cancer 48, 1221–1228 (1981).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecologic Oncology, University of Miami, Miami, Florida, USA

    Anne T. O’Meara, Bernd-Uwe Sevin & James Perras

Authors
  1. Anne T. O’Meara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernd-Uwe Sevin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Perras
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Miami, Coral Gables, Florida, USA

    Elli Kohen  & Joseph G. Hirschberg  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

O’Meara, A.T., Sevin, BU., Perras, J. (1996). The Analysis of Drug-Induced Cell Cycle Perturbations by Flow Cytometry. In: Kohen, E., Hirschberg, J.G. (eds) Analytical Use of Fluorescent Probes in Oncology. NATO ASI Series, vol 286. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5845-3_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5845-3_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7679-8

  • Online ISBN: 978-1-4615-5845-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation