Sister Chromatid Exchange Analysis in Lymphocytes

  • James W. Allen
  • Karen Brock
  • James Campbell
  • Yousuf Sharief
Part of the Topics in Chemical Mutagenesis book series (TCM, volume 2)


Sister chromatid exchanges (SCEs) are generally considered to arise from breakage and recombination of sister chromatid segments at homologous loci.(1) Although the fundamental nature of SCE is not well understood, interests in its frequency have been central both to historical and current studies. Early autoradiographic techniques used to detect this phenomenon were applied for a variety of investigations into its spontaneous and irradiationrelated incidences in somatic and germ cells.(2,3) Nearly a decade ago technically simpler bromodeoxyuridine (BrdUrd)-differential staining methodology was developed in a cultured human lymphocyte system and shown to provide much superior resolving power.(4) Chemical mutagens were clearly demonstrated to induce SCEs at significantly lower doses than those required to cause chromosome aberrations.(5,6) This observation coincided with timely autoradiographic determinations of mutagen action in SCE formation(7,8) and set a new course of emphasis — SCE induction stemming from exposure to environmental agents. The BrdUrd methodology has since been extended to a wide variety of in vitro and in vivo cellular systems, and hundreds of SCE induction trials have implicated numerous chemical, physical (i.e., UV irradiation), and biological (i.e., virus) agents in the production of this effect(9,10) A recent summary evaluation of accumulated results has concluded that most chemical carcinogens induce SCEs, the test being particularly sensitive to agents that cause DNA adducts.(1)


Sister Chromatid Human Lymphocyte Chromosome Aberration Sister Chromatid Exchange Differential Staining 
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  1. 1.
    S. A. Latt, J. Allen, S. Bloom, A. Carrano, E. Falke, D. Kram, E. Schneider, R. Schreck, R. Tice, B. Whitfield, and S. Wolff, Sister-chromatid exchanges: A report of the Gene-Tox Program, Mutat. Res. 87, 17–62 (1981).PubMedGoogle Scholar
  2. 2.
    G. Marin and D. M. Prescott, The frequency of sister chromatid exchanges following exposure to varying doses of 3H-thymidine or X-rays, J. Cell Biol. 21, 159–167 (1964).PubMedCrossRefGoogle Scholar
  3. 3.
    J. H. Taylor, Distribution of tritium-labeled DNA among chromosomes during meiosis, J. Cell Biol. 25, 57–67 (1965).PubMedCrossRefGoogle Scholar
  4. 4.
    S. A. Latt, Microfluorometric detection of DNA replication in human metaphase chromosomes, Proc. Natl. Acad. Sci. USA 70, 3395–3399 (1973).PubMedCrossRefGoogle Scholar
  5. 5.
    S. A. Latt, Sister chromatid exchanges, indices of human chromosome damage and repair: Detection by fluorescence and induction by mitomycin C, Proc. Natl. Acad. Sci. USA 71, 3162–3166 (1974).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Perry and H. J. Evans, Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange, Nature 258, 121–124 (1975).PubMedCrossRefGoogle Scholar
  7. 7.
    S. Wolff, J. Bodycote, and R. B. Painter, Sister chromatid exchanges induced in Chinese hamster cells by UV irradiation of different stages of the cell cycle: The necessity for cells to pass through S, Mutat. Res. 25, 73–81 (1974).PubMedCrossRefGoogle Scholar
  8. 8.
    H. Kato, Induction of sister chromatid exchanges by chemical mutagens and its possible relevance to DNA repair, Exp. Cell Res. 85, 239–247 (1974).PubMedCrossRefGoogle Scholar
  9. 9.
    P. E. Perry, in: Chemical Mutagens — Principles and Methods for Their Detection (F. J. de Serres and A. Hollaender, eds.), Vol. 6, pp. 1–39, Plenum Press, New York (1980).Google Scholar
  10. 10.
    S. A. Latt, R. R. Schreck, K. S. Loveday, C. P. Dougherty, and C. F. Shuler, in: Advances in Human Genetics (H. Harris and K. Hirschhorn, eds.), Vol. 10, pp. 267–331, Plenum Press, New York (1980).Google Scholar
  11. 11.
    J. W. Allen, in: Progress and Topics in Cytogenetics (A. A. Sandberg, ed.), pp. 297–311, Alan R. Liss, New York (1982).Google Scholar
  12. 12.
    D. G. Stetka, in: Progress and Topics in Cytogenetics (A. A. Sandberg, ed.), pp. 99–114, Alan R. Liss, New York (1982).Google Scholar
  13. 13.
    R. J. Reynolds, A. T. Natarajan, and P. H. M. Lohman, Micrococcus luteus UV-endonuclease sensitive sites and sister-chromatid exchanges in Chinese hamster ovary cells, Mutat. Res. 64, 353–356 (1979).PubMedGoogle Scholar
  14. 14.
    R. B. Painter, A replication model for sister-chromatid exchange, Mutat. Res. 70, 337–341 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    J. E. Cleaver, Correlations between sister chromatid exchange frequencies and replicon sizes. A model for the mechanism of SCE production, Exp. Cell Res. 136, 27–30 (1981).PubMedCrossRefGoogle Scholar
  16. 16.
    A. V. Carrano, L. H. Thompson, P. A. Lindl, and J. L. Minkler, Sister chromatid exchange as an indicator of mutagenesis, Nature 271, 551–553 (1978).PubMedCrossRefGoogle Scholar
  17. 17.
    D. Turnbull, N. C. Popescu, J. A. DiPaolo, and B. C. Myhr, cis-Platinum (II) diamine dichloride causes mutation, transformation, and sister chromatid exchanges in cultured mammalian cells, Mutat. Res. 66, 267–275 (1979).PubMedCrossRefGoogle Scholar
  18. 18.
    H. J. Evans, and Vijayalaxmi, Induction of 8-azaguanine resistance and sister chromatid exchange in human lymphocytes exposed to mitomycin C and X rays in vitro, Nature 292, 601–604 (1981).PubMedCrossRefGoogle Scholar
  19. 19.
    M. O. Bradley, I. C. Hsu, and C. C. Harris, Relationships between sister chromatid exchange and mutagenicity, toxicity, and DNA damage, Nature 282, 318–320 (1979).PubMedCrossRefGoogle Scholar
  20. 20.
    H. W. Rudiger, F. Kohl, W. Mangels, P. von Wichert, C. R. Bartram, W. Wohler, and E. Passarge, Benzpyrene induces sister chromatid exchanges in cultured human lymphocytes, Nature 262, 290–292 (1976).PubMedCrossRefGoogle Scholar
  21. 21.
    J. M. Hopkin and P. E. Perry, Benzo[a]pyrene does not contribute to the SCEs induced by cigarette smoke condensate, Mutat. Res. 77, 377–381 (1980).PubMedCrossRefGoogle Scholar
  22. 22.
    H. Norppa, M. Sorsa, P. Pfaffli, and H. Vainio, Styrene and styrene oxide induce SCEs and are metabolized in human lymphocyte cultures, Carcinogenesis 1, 357–361 (1980).PubMedCrossRefGoogle Scholar
  23. 23.
    A. D. Bloom, A. V. Carrano, P. G. Archer, M. Bender, J. G. Brewen, and R. J. Preston, in: Guidelines for Studies of Human Populations Exposed to Mutagenic and Reproductive Hazards (A. D. Bloom, ed.), pp. 3-35, March of Dimes Birth Defects Foundation, White Plains, New York (1981).Google Scholar
  24. 24.
    J. G. Brewen, Cytogenetic monitoring in the workplace: Is it scientifically sound and practical? Hazardous Materials Management J. 1, 28–33 (1980).Google Scholar
  25. 25.
    B. Lambert, in: Lymphocyte Stimulation (A. Castellani, ed.), pp. 119–130, Plenum Press, New York (1980).CrossRefGoogle Scholar
  26. 26.
    S. M. Galloway and R. R. Tice, in: The Genotoxic Effects of Airborne Agents (R. R. Tice, D. L. Costa, and K. M. Schaich, eds.), pp. 463–488, Plenum Press, New York (1982).CrossRefGoogle Scholar
  27. 27.
    J. H. Taylor, P. S. Woods, and W. L. Hughes, The organization and duplication of chromosomes as revealed by autoradiographic studies using tritium-labeled thymidine, Proc. Natl. Acad. Sci. USA 43, 122–128 (1957).PubMedCrossRefGoogle Scholar
  28. 28.
    P. Perry and S. Wolff, New Giemsa method for the differential staining of sister Chromatide, Nature 251, 156–158 (1974).PubMedCrossRefGoogle Scholar
  29. 29.
    K. Goto, S. Maeda, Y. Kano, and T. Sugiyama, Factors involved in differential Giemsastaining of sister chromatids, Chromosoma 66, 351–359 (1978).PubMedCrossRefGoogle Scholar
  30. 30.
    N. R. Ling and J. E. Kay, Lymphocyte Stimulation, American Elsevier, New York (1975).Google Scholar
  31. 31.
    M. F. Greaves, J. J. T. Owen, and M. C. Raff, T and B Lymphocytes, American Elsevier, New York (1974).Google Scholar
  32. 32.
    J. W. Allen, C. F. Shuler, and S. A. Latt, Bromodeoxyuridine tablet methodology for in vivo studies of DNA synthesis, Somatic Cell Genet. 4, 393–405 (1978).PubMedCrossRefGoogle Scholar
  33. 33.
    C. C. Huang and M. Furukawa, Sister chromatid exchanges in human lymphoid cell lines cultured in diffusion chambers in mice, Exp. Cell Res. 111, 458–461 (1978).PubMedCrossRefGoogle Scholar
  34. 34.
    Y. Shiraishi and A. A. Sandberg, Effects of various chemical agents on sister chromatid exchanges, chromosome aberrations, and DNA repair in normal and abnormal human lymphoid cell lines, J. Natl. Cancer Inst. 62, 27–33 (1979).PubMedGoogle Scholar
  35. 35.
    C. Fonatsch, M. Schaadt, and V. Diehl, Sister chromatid exchange in cell lines from malignant lymphomas (lymphoma lines), Hum. Genet. 52, 107–118 (1979).PubMedCrossRefGoogle Scholar
  36. 36.
    H. Tohda, A. Oikawa, T. Kawachi, and T. Sugimura, Induction of sister-chromatid exchanges by mutagene from amino acid and protein pyrolysates, Mutat. Res. 77, 65–69 (1980).PubMedCrossRefGoogle Scholar
  37. 37.
    R. Tice, P. Thome, and E. L. Schneider, Bisack analysis of the phytohaemagglutinin-induced proliferation of human peripheral lymphocytes, Cell Tiss. Kinet. 12, 1–9 (1979).Google Scholar
  38. 38.
    S. Takehisa and S. Wolff, Sister-chromatid exchanges induced in rabbit lymphocytes by 2-aminofluorene and 2-acetylaminofluorene after in vitro and in vivo metabolic activation, Mutat. Res. 58, 321–329 (1978).PubMedCrossRefGoogle Scholar
  39. 39.
    H.-J. Heiniger, B. Taylor, E. Hards, and H. Meier, Heritability of the phytohemagglutinin responsiveness of lymphocytes and its relationship to leukemogenesis, Cancer Res. 35, 825–831 (1975).PubMedGoogle Scholar
  40. 40.
    B. G. Leventhal, D. S. Waldorf, and N. Talal, Impaired lymphocyte transformation and delayed hypersensitivity in Sjogren’s Syndrome, J. Clin. Invest. 46, 1338–1345 (1967)PubMedCrossRefGoogle Scholar
  41. 41.
    P. E. Crossen and W. F. Morgan, Lymphocyte proliferation in Down’s Syndrome measured by sister chromatid differential staining, Hum. Genet. 53, 311–313 (1980).PubMedGoogle Scholar
  42. 42.
    P. E. Crossen and W. F. Morgan, Occurrence of 1st division metaphases in human lympho-cyte cultures, Hum. Genet. 41, 97–100 (1978).PubMedCrossRefGoogle Scholar
  43. 43.
    B. Santesson, K. Lindahl-Kiessling, and A. Mattsson, SCE in B and T lymphocytes. Possible implications for Bloom’s syndrome, Clin. Genet. 16, 133–135 (1979).PubMedCrossRefGoogle Scholar
  44. 44.
    J. L. Schwartz and M. E. Gaulden, The relative contributions of B and T lymphocytes in the human peripheral blood mutagen test system as determined by cell survival, mutagenic stimulation, and induction of chromosome aberrations by radiation, Environ. Mutagen. 2, 473–485 (1980).PubMedCrossRefGoogle Scholar
  45. 45.
    H. J. Evans and Vijayalaxmi, Storage enhances chromosome damage after exposure of human leukocytes to mitomycin C, Nature 284, 370–372 (1980).PubMedCrossRefGoogle Scholar
  46. 46.
    E. Giulotto, A. Mottura, R. Giorgi, L. deCarli, and F. Nuzzo, Frequencies of sister chromatid exchanges in relation to cell kinetics in lymphocyte cultures, Mutat. Res. 70, 343–350 (1980).PubMedCrossRefGoogle Scholar
  47. 47.
    A. V. Carrano. J. L. Minkler, D. G. Stetka, and D. H. Moore, II, Variation in the baseline sister chromatid exchange frequency in human lymphocytes, Environ. Mutagen. 2, 325–337 (1980).PubMedCrossRefGoogle Scholar
  48. 48.
    B. Beek and G. Obe, Sister chromatid exchanges in human leukocyte chromosomes: Spontaneous and induced frequencies in early and late-proliferating cells in vitro, Hum. Genet. 49, 51–61 (1979).PubMedGoogle Scholar
  49. 49.
    W. F. Morgan and P. E. Crossen, The incidence of sister chromatid exchanges in cultured human lymphocytes, Mutat. Res. 42, 305–312 (1977).PubMedCrossRefGoogle Scholar
  50. 50.
    A. J. Snope and J. M. Rary, Cell-cycle duration and sister chromatid exchange frequency in cultured human lymphocytes, Mutat. Res. 63, 345–349 (1979).PubMedCrossRefGoogle Scholar
  51. 51.
    E. L. Schneider and B. Gilman, Sister chromatid exchanges and aging III. The effect of donor age on mutagen-induced sister chromatid exchange in human diploid fibroblasts, Hum. Genet. 46, 57–63 (1979).PubMedCrossRefGoogle Scholar
  52. 52.
    Y. Nakanishi, D. Kram, and E. L. Schneider, Aging and sister chromatid exchange. IV. Reduced frequencies of mutagen-induced sister chromatid exchanges in vivo in mouse bone marrow cells with aging, Cytogenet. Cell Genet. 24, 6167 (1979).CrossRefGoogle Scholar
  53. 53.
    R. R. Tice, D. L. Costa, and R. T. Drew, Cytogenetic effects of inhaled benzene in murine bone marrow: Induction of sister chromatid exchanges, chromosomal aberrations and cellular proliferation inhibition in DBA/2 mice, Proc. Natl. Acad. Sci. USA 77, 2148–2152 (1979).CrossRefGoogle Scholar
  54. 54.
    J. M. Hopkin and H. J. Evans, Cigarette smoke condensates damage DNA in human lymphocytes, Nature 279, 241–232 (1979).PubMedCrossRefGoogle Scholar
  55. 55.
    R. L. Davidson, E. R. Kaufman, C. P. Dougherty, A. M. Ouellette, C. M. Difolco, and S. A. Latt, Induction of sister chromatid exchanges by BudR is largely independent of the BudR content of DNA, Nature 284, 74–76 (1980).PubMedCrossRefGoogle Scholar
  56. 56.
    D. Anderson, C. R. Richardson, I. F. H. Purchase, H. J. Evans, and M. L. O’Riordan, Chromosomal analysis in vinyl chloride exposed workers: Comparison of the standard technique with the sister chromatid exchange technique, Mutat. Res. 83, 137–144 (1981).PubMedCrossRefGoogle Scholar
  57. 57.
    F. Apelt, J. Kolin-Gerresheim, and M. Bauchinger, Azathioprine, a clastogen in human cells? Analysis of chromosome damage and SCE in lymphocytes after exposure in vivo and in vitro, Mutat. Res. 88, 61–72 (1981).PubMedCrossRefGoogle Scholar
  58. 58.
    J. A. Mannick, M. Constantian, D. Pardridge, I. Saporoschetz, and A. Badger, Improvement of phytohemagglutinin reponsiveness of lymphocytes from cancer patients after washing in vitro, Cancer Res. 37, 3066–3070 (1977).PubMedGoogle Scholar
  59. 59.
    A. D. White and L. C. Hasketh, A method utilizing human lymphocytes with in vitro metabolic activation for assessing chemical mutagenicity by sister-chromatid exchange analysis, Mutat. Res. 68, 283–291 (1980).Google Scholar
  60. 60.
    D. G. Stetka, J. Minkler, and A. V. Carrano, 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 (1978).PubMedCrossRefGoogle Scholar
  61. 61.
    A. F. McFee and M. N. Sherrill, Species variation in BrdUrd-induced sister-chromatid exchanges, Mutat. Res. 62, 131–138 (1979).PubMedCrossRefGoogle Scholar
  62. 62.
    G. L. Erexson, J. L. Wilmer, and A. D. Kligerman, Analysis of sister chromatid exchange and cell-cycle kinetics in mouse T-and B-lymphocytes from peripheral blood cultures, Mutat. Res. 109, 271–281 (1983).PubMedCrossRefGoogle Scholar
  63. 63.
    A. D. Kligerman, J. L. Wilmer, and G. L. Erexson, Characterization of a rat lymphocyte culture system for assessing sister chromatid exchange after in vivo exposure to genotoxic agents, Environ. Mutagen. 3, 531–543 (1981).PubMedCrossRefGoogle Scholar
  64. 64.
    M. Ohtsuru, Y. Ishii, S. Takai, H. Higashi, and G. Kosaki, Sister chromatid exchanges in lymphocytes of cancer patients receiving mitomycin C treatment, Cancer Res. 40, 477–480 (1980).PubMedGoogle Scholar
  65. 65.
    Y. Ishii and M. A. Bender, Caffeine inhibition of prereplication repair of mitomycin C-induced DNA damage in human peripheral lymphocytes, Mutat. Res. 51, 419–425 (1978).PubMedCrossRefGoogle Scholar
  66. 66.
    G. L. Littlefield, S. P. Colyer, A. M. Sayer, and R. J. Dufrain, Sister-chromatid exchanges in human lymphocytes exposed during G0 to four classes of DNA-damaging chemicals, Mutat. Res. 67, 259–269 (1979).PubMedCrossRefGoogle Scholar
  67. 67.
    B. Lambert, A. Bredberg, W. McKenzie, and M. Sten, Sister-chromatid exchange in human populations: The effect of smoking, drug treatment and occupational exposure, Cytogen. Cell Genet. 33, 62–67 (1982).CrossRefGoogle Scholar
  68. 68.
    W. McKenzie and B. Lambert, Induction and reduction of sister chromatid exchange by CCNU in human lymphocytes in vitro, Cancer Genet. Cytogenet. 9, 261–271 (1983).PubMedCrossRefGoogle Scholar
  69. 69.
    G. T. Roberts and J. W. Allen, Tissue-specific induction of sister-chromatid exchanges by ethyl carbamate in mice, Environ. Mutagen. 2, 17–26 (1980).PubMedCrossRefGoogle Scholar
  70. 70.
    M. Cheng, M. K. Conner, and Y. Alarie, Multicellular in vivo sister-chromatid exchanges induced by urethane, Mutat. Res. 88, 223–231 (1981).PubMedCrossRefGoogle Scholar
  71. 71.
    J. Ashby, in: Evaluation of Short-Term Tests for Carcinogens (F. J. deSerres and J. Ashby, eds.), pp. 112–171, Elseivier/North-Holland, New York (1981).Google Scholar
  72. 72.
    J. W. Allen, Y. Sharief, and R. J. Langenbach, in: The Genotoxic Effects of Airborne Agents (R. R. Tice, ed.), pp. 443–460, Plenum Press, New York (1982).CrossRefGoogle Scholar
  73. 73.
    I. Csukas, E. Gungl, F. Antoni, G. Vida, and F. Solymosy, Role of of metabolic activation in the sister chromatid exchange-inducing activity of ethyl carbamate (urethane) and vinyl carbamate, Mutat. Res. 89, 75–82 (1981).PubMedCrossRefGoogle Scholar
  74. 74.
    G. A. Dahl, J. A. Miller, and E. C. Miller, Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate, Cancer Res. 38, 3793–3804 (1978).PubMedGoogle Scholar
  75. 75.
    J. W. Allen, R. Langenbach, S. Nesnow, K. Sasseville, S. Leavitt, J. Campbell, K. Brock, and Y. Sharief, Comparative genotoxicity studies of ethyl carbamate and related chemicals: further support for vinyl-carbamate as a proximate carcinogenic metabolite, Carcinogenesis 3, 1437–1441 (1982).PubMedCrossRefGoogle Scholar
  76. 76.
    F. Fumes-Cravioto, C. Zapata-Gayon, B. Kolmodin-Hedman, B. Lambert, J. Lindsten, E. Norberg, M. Nordenskjold, R. Olin, and A. Swensson, in: Mutagen-Induced Chromosome Damage in Man (H. J. Evans and D. C. Lloyd, eds), Edinburgh University Press, Edinburgh, Scotland (1978).Google Scholar
  77. 77.
    J. Kowalczyk, Sister-chromatid exchanges in children treated with nalidixic acid, Mutat. Res. 77, 371–375 (1980).PubMedCrossRefGoogle Scholar
  78. 78.
    M. Kucerova, Z. Polivkova, and J. Batora, Comparative evaluation of the frequency of chromosomal aberrations and the SCE numbers in peripheral lymphocytes of workers occupationally exposed to vinyl chloride monomer, Mutat. Res. 67, 97–100 (1979).PubMedCrossRefGoogle Scholar
  79. 79.
    V. F. Garry, J. Hozier, D. Jacobs, R. L. Wade, and D. G. Gray, Ethylene oxide: Evidence of human chromosomal effects, Environ. Mutagen. 1, 375–382 (1979).PubMedCrossRefGoogle Scholar
  80. 80.
    T. Raposa, Sister-chromatid exchange studies for monitoring DNA damage and repair capacity after cytostatics in vitro and in lymphocytes of leukemic patients under cytostatic therapy, Mutat. Res. 57, 241–251 (1978).PubMedCrossRefGoogle Scholar
  81. 81.
    U. Haglund, S. Hayder, and L. Zech, Sister-chromatid exchanges and chromosome aberrations in children after treatment for malignant lymphoma, Cancer Res. 40, 4786–4790 (1980).PubMedGoogle Scholar
  82. 82.
    K. L. Triman, M. T. Davisson, and T. H. Roderick, A method for preparing chromosomes from peripheral blood in the mouse, Cytogenet. Cell Genet. 15, 166–176 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • James W. Allen
    • 1
  • Karen Brock
    • 2
  • James Campbell
    • 2
  • Yousuf Sharief
    • 2
  1. 1.Genetic Toxicology Division, Health Effects Research LaboratoryU.S. Environmental Protection AgencyUSA
  2. 2.Northrop Services, Inc.USA

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