Sister Chromatid Exchange Frequency and Cell Cycle Kinetics in Cancer Patients Treated with Cytostatic Drugs

  • Narendra P. Singh
  • Steven M. D’Ambrosio


The ability of various cytostatic drugs to induce sister chromatid exchanges (SCE) and to alter the progression of cells through mitosis was analyzed in lymphocytes cultured from cancer patients following various in vivo chemotherapy treatments. Control individuals exhibited 4.87 ± 0.08 SCEs per metaphase. Patients being treated with cyclophosphamide (CP), mitomycin C (MMC), and/or cisplatinum (CPT) in combination with other drugs exhibited 3-to 5-fold greater levels of SCEs. Other cytostatic drugs: the plant alkaloids; vincristine (VCR); and homoharringtonine (HHT); the antibiotic, adriamycin (ADM); the folic acid antagonist, methotrexate (MTX); and the nucleotide analogue, dihydroazacytidine (HAC) did not appear to induce SCE levels significantly above controls. Most of the cytostatic drugs used in cancer patients appeared to delay the progression of cells through mitosis. All the drug protocols which included a known DNA-damaging agent induced SCE. There was no relationship between SCE and cell cycle kinetics. Thus, SCE appears to be a sensitive assay for monitoring the in vivo exposure of individuals to genotoxic agents.


None None Large Cell Carci Noma Cytostatic Drug Genotoxic Agent Drug Protocol 
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  1. 1.
    Rosner, F. (1976) Acute leukemia as a delayed consequence of cancer chemotherapy. Cancer 37;1033–1036.PubMedCrossRefGoogle Scholar
  2. 2.
    Perry, P.E., and H.J. Evans (1975) Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. Nature 258:121–125.PubMedCrossRefGoogle Scholar
  3. 3.
    Perry, P.E. (1980) Chemical mutagens and sister chromatid exchange. In Chemical Mutagens, Vol. 6, F.J. de Serres and A. Hollaender, eds. Plenum Press, New York, pp. 1–40.CrossRefGoogle Scholar
  4. 4.
    Stetka, D.G., J. Minkler, and A.V. Carrano (1978) Induction of long-lived chromosome damage, as manifested by sister chromatid exchange, in lymphocytes of animals exposed to mitomycin C. Mutat. Res. 51:383–396.PubMedCrossRefGoogle Scholar
  5. 5.
    Littlefield, L.G., S.P. Colyer, and R.J. DuFrain (1980) Compar ison of sister chromatid exchanges in human lymphocytes after Go exposure to mitomycin C in vivo vs. in vitro. Mutat. Res.69:191–197.PubMedCrossRefGoogle Scholar
  6. 6.
    Brown, R.L., and P.E. Crossen (1976) Increased incidence of sister chromatid exchanges in Rauscher leukemia virus infected mouse fibroblast. Exp. Cell Res. 103:418–420.PubMedCrossRefGoogle Scholar
  7. 7.
    Nichols, W.W., C.I. Bradl, L.H. Toji, M. Godley, and M. Segawa (1978) Induction of sister chromatid exchanges by transforma tion with SV40. Cancer Res. 38:960–964.PubMedGoogle Scholar
  8. 8.
    Brown, E.H., and C. Basilico (1982) Induction of sister chromatid exchange by polyoma large viral tumor antigen in transformed rat fibroblasts. Cancer Res. 42:1909–1912.PubMedGoogle Scholar
  9. 9.
    Abe, S., and M. Sasaki (1977) Chromosome aberrations and sister chromatid exchanges in Chinese hamster cells exposed to various chemicals. J. Natl. Cancer Inst. 58:1635–1641.PubMedGoogle Scholar
  10. 10.
    Carrano, A.V., L.H. Thompson, P.A. Linde, and J.L. Minkle (1978) Sister chromatid exchange as an indicator of mutagens. Nature 271:551–553.PubMedCrossRefGoogle Scholar
  11. 11.
    Kato, H., and H. Shimada (1975) Sister chromatid exchanges induced by mitomycin C, a new method of detecting DNA damge at chromosomal level. Mutat. Res. 23:459–464.Google Scholar
  12. 12.
    Popescu, N.C., D. Turnbull, and J.A. DiPaolo (1977) Sister chromatid exchange and chromosome aberration analysis with the use of several carcinogens and non-carcinogens brief communication. J. Natl. Cancer Inst. 59:289–293.PubMedGoogle Scholar
  13. 13.
    Ohtsuru, M., Y. Ishii, S. Takai, H. Higashi, and G. Kosaki (1980) Sister chromatid exchanges in lymphocytes of cancer patients receiving mitomycin treatment. Cancer Res. 40:477–480.PubMedGoogle Scholar
  14. 14.
    Banerjee, A., and W.F. Benedict (1979) Production of sister chromatid exchanges by various chemotherapeutic agents. Cancer Res. 39:797–799.PubMedGoogle Scholar
  15. 15.
    Benedict, W.F., A. Banerjee, and N. Venkatesan (1978) Cyclophosphamide induced oncogenic transformation, chromosomal breakage and sister chromatid exchange following microsomal activation. Cancer Res. 38:2922–2924.PubMedGoogle Scholar
  16. 16.
    Raposa, T. (1978) Sister chromatid exchange studies for monitoring DNA damage and repair capacity after cytostatics in vitro and in lymphocytes of leukaemic patients under cytostatic therapy. Mutat. Res. 57:241–251.PubMedCrossRefGoogle Scholar
  17. 17.
    Parkes, J.J.G., and S. Scott (1982) A quantitative comparison of cytogenetic effects of anti-tumor agents. Cytogenet. Cell Genet. 33:27–34.PubMedCrossRefGoogle Scholar
  18. 18.
    Nevstad, N.P. (1977) Sister chromatid exchange and chromosomal aberrations induced in human lymphocytes by the cytostatic drug adriamycin in vivo and in vitro. Mutat. Res. 57:253–258.Google Scholar
  19. 19.
    Ohisuru, M., Y. Ishii, S. Takai, and G. Kosake (1982) Sister chromatid exchanges in lymphocytes of a patient treated with cyclophosphamide and vincristine for non-Hodgkins lymphoma. Gann 73(3):433–438.Google Scholar
  20. 20.
    Abdel-Fadil, M.R., C.G. Palmer, and H. Heerema (1982) Effect of temperature variation on sister chromatid exchange and cell cycle duration in cultured human lymphocytes. Mutat. Res.104:267–273.PubMedCrossRefGoogle Scholar
  21. 21.
    Snope, A.J., and J.M. Rary (1979) Cell cycle duration and sister chromatid exchange frequency in cultured human lympho cytes. Mutat. Res. 63:345–349.PubMedCrossRefGoogle Scholar
  22. 22.
    Goto, K., S. Maeda, Y. Kano, and T. Sugiyoma (1978) Factors involved in differential Giemsa staining of sister chromatids. Chromosoma 66:351–359.PubMedCrossRefGoogle Scholar
  23. 23.
    Crossen, P.E. (1982) Variation in sensitivity of human lymphocytes to DNA-damaging agents measured by sister chromatid exchange frequency. Human Genet. 60:19–23.CrossRefGoogle Scholar
  24. 24.
    Musilova, J., K. Michalova, and J. Urban (1979) Sister chromatid exchanges and chromosomal breakage in patients treated with cytostatics. Mutat. Res. 67:289–294.PubMedCrossRefGoogle Scholar
  25. 25.
    Littlefield, L.G., S.P. Colyer, A.M. Sayer, and R.J. DuFrain (1979) Sister chromatid exchanges in human lymphocytes exposed during Go to four classes of DNA damaging chemicals. Mutat. Res. 67:259–269.PubMedCrossRefGoogle Scholar
  26. 26.
    Andersen, K.S. (1979) Platinum (II) complexes generate frame-shift mutations in test strains of Salmonella typhimurium. Mutat. Res. 67:209–214.PubMedCrossRefGoogle Scholar
  27. 27.
    Turnbull, D., N.C. Popescu, J.A. DiPaolo, and B.C. Myhr (1979) Cis-platinum (II) diamine dichloride causes mutation, transformation and sister chromatid exchanges in cultured mammalian cells. Mutat. Res. 66:267–275.PubMedCrossRefGoogle Scholar
  28. 28.
    Zwelling, L.A., M.O. Bradley, N.A. Sharkey, T. Anderson, and K.W. Kohn (1979) Mutagenicity, cytotoxicity and DNA crosslink-ing in V-79 Chinese hamster cells treated with cis and trans-Pt(II) diamminedichloride. Mutat. Res. 67:271–280.PubMedCrossRefGoogle Scholar
  29. 29.
    Oredsson, S.M., D.F. Dean, and L.J. Marton (1982) Decreased cytotoxicity of cis-diamminedichlor-platinum (II) by -difluor-omethylornithine depletion of polyamines in 9L rat brain tumor cells in vitro. Cancer Res. 42:1296–1299.PubMedGoogle Scholar
  30. 30.
    Wiencke, J.K., J. Cervenka, B.J. Kennedy, J. Prlina, and R. Gorlin (1982) Sister-chromatid exchange induction by cisplatinum/adriamycin cancer chemotherapy. Mutat. Res. 104:131–136.PubMedCrossRefGoogle Scholar
  31. 31.
    Cephalotaxus Research Coordinating Group (1976) Cephalotaxine esters in the treatment of acute leukemia: A preliminary clinical assessment. Chinese Med. J. 2(4):263–272.Google Scholar
  32. 32.
    Ishii, Y. (1981) Nature of the mitomycin C induced lesion causing sister chromatid exchange. Mutat. Res. 91:51–55.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Narendra P. Singh
    • 1
  • Steven M. D’Ambrosio
    • 1
  1. 1.Department of Radiology College of MedicineOhio State UniversityColumbusUSA

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