Removal and Persistence of SCE-Inducing Damage in Human Lymphocytes in Vitro

  • Bo Lambert
  • Margareta Sten
  • Dennis Hellgren


The ability to induce sister chromatid exchanges (SCEs) is a well-known property of many DNA-damaging agents (for review see Refs. 20,32). There is no conclusive evidence that any particular type of DNA lesion is more frequently involved in SCE induction than other lesions (e.g., Refs. 3,11,31), although, in general, agents inducing DNA interstrand cross-links appear to be very potent SCE inducers (1,8,13,24).


Chinese Hamster Ovary Cell Human Lymphocyte Sister Chromatid Exchange Nitrogen Mustard Untreated Control Culture 


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  1. 1.
    Bredberg, A., and B. Lambert (1983) Induction of SCE by DNA cross-links in human fibroblasts exposed to 8-MOP and UVA irra-diation. Mutat. Res. 118:191–204.PubMedCrossRefGoogle Scholar
  2. 2.
    Darzynkiewicz, Z. (1971) Radiation-induced DNA synthesis in normal and stimulated human lymphocytes. Exp. Cell Res. 69: 356–360.PubMedCrossRefGoogle Scholar
  3. 3.
    Duncan, A.M.V., and H.J. Evans (1982) Molecular lesions involved in the induction of sister-chromatid exchange. Mutat. Res. 105:423–427.PubMedCrossRefGoogle Scholar
  4. 4.
    Ericksson, L.C., M.O. Bradley, J.M. Ducore, R.A.G. Ewig, and K.W. Kohn (1980) DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas. Proc. Natl. Acad. Sci., USA 77:467–471.CrossRefGoogle Scholar
  5. 5.
    Erickson, L.C., G. Laurent, N.A. Sharkey, and K.W. Kohn (1980) DNA cross-linking and monoadduct repair in nitrosourea-treated human tumor cells. Nature (Lond.) 288:727–729.CrossRefGoogle Scholar
  6. 6.
    Evans, H.J., and Vijayalaxmi (1982) Storage enhances chromosome damage after exposure of human leukocytes to mitomycin C. Nature (Lond.) 284:370–372.CrossRefGoogle Scholar
  7. 7.
    Ewig, R.A.G., and K.W. Kohn (1977) DNA damage and repair in mouse leukemia LI210 cells treated with nitrogen mustard, 1,3-Bis(2-chloroethyl)-l-nitrosourea, and other nitrosoureas. Can cer Res. 37:2114–2122.Google Scholar
  8. Fujiwara, Y. (1982) Defective repair of mitomycin C crosslinks in Fanconi’s anemia and loss in confluent normal human and xer-oderma pigmentosum cells. Biochim. Biophys. Acta 699:217–225.PubMedCrossRefGoogle Scholar
  9. 9.
    Gebhart, E., B. Windolph, and F. Wopfner (1980) Chromosome studies on lymphocytes of patients under cytostatic therapy. II. Studies using the BUDR-labelling technique in cytostatic interval therapy. Human Genet. 56;157–167.CrossRefGoogle Scholar
  10. 10.
    Hedner, K., F. Mitelman, and R.W. Pero (1983) Sister chromatid exchanges in human lymphocytes after a non-S-phase incubation period to allow excision DNA repair -In vitro exposure to N-acetoxy-2-acetylaminofluorene and ethylene oxide. In Aspects on Sister Chromatid Exchange in Human Lymphocytes, K. Hedner, Thesis. University of Lund, Sweden.Google Scholar
  11. 11.
    Heflich, R.H., D.T. Beranek, R.L. Kodell, and S.M. Morris (1982) Induction of mutations and sister chromatid exchanges in Chinese hamster ovary cells by ethylating agents. Mutat. Res. 106:147–161.PubMedCrossRefGoogle Scholar
  12. 12.
    Ishii, Y., and M.A. Bender (1978) Factors influencing the fre quency of mitomycin C-induced sister chromatid exchanges in 5-bromodeoxyuridine-substituted human lymphocytes in culture. Mutat. Res. 51:411–418.PubMedCrossRefGoogle Scholar
  13. 13.
    Kano, Y., and Y. Fujiwara (1981) Role of DNA interstrand cross-linking: Its repair in the induction of sister chromatid exchange and a higher induction in Fanconi’s anemia cells. Mutat. Res. 81:365–375.PubMedCrossRefGoogle Scholar
  14. 14.
    Kohn, K.W. (1977) Interstrand cross-linking of DNA by 1,3-Bis-(2-chloroethyl)-l-nitrosourea and other l-(2-haloethyl)-l-nitrosoureas. Cancer Res. 37:1450–1454.PubMedGoogle Scholar
  15. 15.
    Lambert, B., A. Lindblad, K. Holmberg, and D. Francesconi (1982) The use of sister chromatid exchange to monitor human populations for exposure to toxicologically harmful agents. In Sister Chromatid Exchange, S. Wolff, ed. John Wiley & Sons, New York, pp. 149–182.Google Scholar
  16. 16.
    Lambert, B., U. Ringborg, A. Lindblad, and M. Sten (1979) The effects of DTIC, melphalan, actinomycin D and CCNU on the frequency of sister chromatid exchanges in peripheral lymphocytes of melanoma patients. In Adjuvant Therapy of Cancer II, S.E. Jones and S.E. Salmon, eds. Grune & Stratton, New York, pp. 55–62.Google Scholar
  17. 17.
    Lambert, B., M. Sten, D. Hellgren, and D. Francesconi (1984) Different SCE-inducing effects of HN2 and MMS in early and late G1, in human lymphocytes. Mutat. Res. 139:71–77.PubMedCrossRefGoogle Scholar
  18. 18.
    Lambert, B., M. Sten, S. Söderhäll, U. Ringborg, and R. Lewensohn (1983) DNA repair replication DNA breaks and sister chromatid exchange in human cells treated with adriamycin in vitro. Mutat. Res. 111:171–184.PubMedCrossRefGoogle Scholar
  19. 19.
    Lewensohn, R., D. Killander, U. Ringborg, and B. Lambert (1979) Increase of UV-induced DNA repair synthesis during blast transformation of human lymphocytes. Exp. Cell Res. 123:107–110.PubMedCrossRefGoogle Scholar
  20. 20.
    Littlefield, L.G. (1982) Effects of DNA-damaging agents on SCE. In Sister Chromatid Exchange, A.A. Sandberg, ed. Alan R. Liss, New York, pp. 355–394.Google Scholar
  21. 21.
    Littlefield, L.G., S.P. Colyer, and R.J. DuFrain (1983) SCE evaluations in human lymphocytes after GO exposure to mitomycin C. Lack of expression of MMC-induced SCEs in cells that have undergone greater than two in vitro divisions. Mutat. Res. 107:119–130.PubMedCrossRefGoogle Scholar
  22. 22.
    McKenzie. W., and B. Lambert (1983) Induction and reduction of sister chromatid exchange by CCNU in human lymphocytes in vitro. Cancer Genet. Cytogenet. 9:261–271.PubMedCrossRefGoogle Scholar
  23. 23.
    Muscarella, D.E., and S.E. Bloom (1982) The longevity of chemi cally induced sister chromatid exchanges in Chinese hamster ovary cells. Environ. Mutagen. 4:647–655.PubMedCrossRefGoogle Scholar
  24. 24.
    Natarajan, A.T., A.D. Tates, M. Meijers, J. Neuteboom, and N. de Vogel (1983) Induction of sister chromatid exchanges (SCEs) and chromosomal aberrations by mitomycin C and methyl methane-sulfonate in Chinese hamster ovary cells. Mutat. Res. 121:211–223.PubMedCrossRefGoogle Scholar
  25. 25.
    Ockey, C.H. (1981) Methyl methane-sulphonate (MMS) induced SCEs are reduced by the BrdU used to visualise them. Chromosoma 84: 243–256.PubMedCrossRefGoogle Scholar
  26. 26.
    Perticone, P., and B. Lambert (1984) The SCE-frequency in human lymphocytes irradiated with UV-light at different times in G1, (submitted for publication).Google Scholar
  27. 27.
    Ross, W.E., R.A.G. Ewig, and K.W. Kohn (1978) Differences between melphalan and nitrogen mustard in the formation and removal of DNA cross-links. Cancer Res. 38:1502–1506.PubMedGoogle Scholar
  28. 28.
    Sasaki, M.S. (1982) Sister chromatid exchange as a reflection of cellular DNA repair. In Sister Chromatid Exchange, A.A. Sandberg, ed. Alan R. Liss, New York, pp. 135–161.Google Scholar
  29. 29.
    Scudiero, D., A. Norin, P. Karran, and B. Strauss (1976) DNA excision-repair deficiency of human peripheral blood lymphocytes treated with chemical carcinogens. Cancer Res. 36:1397–1403.PubMedGoogle Scholar
  30. 30.
    Stetka, D.G., J. Minkler, and A.V. Carrano (1978) Induction of longlived chromosome damage as manifested by sister chromatid exchange in lymphocytes of animals exposed to mitomycin C. Mutat. Res. 51:383–396.PubMedCrossRefGoogle Scholar
  31. 31.
    Swenson, D.H., P.R. Harbach, and R.J. Trzos (1980) The relationship between alkylation of specific DNA bases and induction of sister chromatid exchange. Carcinogenesis 1:931–936.PubMedCrossRefGoogle Scholar
  32. 32.
    Takehisa, S. (1982) Induction of sister chromatid exchanges by chemical agents. In Sister Chromatid Exchange, S. Wolff, ed. John Wiley & Sons, New York, pp. 87–147.Google Scholar
  33. 33.
    Tice, R.R., and J.B. Schwartzman (1982) Sister chromatid exchange: A measure of DNA lesion persistence. In Sister Chro matid Exchange, A.A. Sandberg, ed. Alan R. Liss, New York, pp. 33–45.Google Scholar
  34. 34.
    Wolff, S. (1978) Chromosomal effects of mutagenic carcinogens and the nature of the lesions leading to sister chromatid exchange. In Mutation Induced Chromosome Damage in Man, H.J. Evans and D.C. Lloyd, eds. Edinburgh University Press, pp. 208–215.Google Scholar
  35. 35.
    Wolff, S., J. Bodycote, and R.B. Painter (1974) Sister chroma tid 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.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Bo Lambert
    • 1
  • Margareta Sten
    • 1
  • Dennis Hellgren
    • 1
  1. 1.Department of Clinical GeneticsKarolinska HospitalStockholmSweden

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