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Persistence of SCE-Inducing Lesions after GO Exposure of Human Lymphocytes to Differing Classes of DNA-Damaging Chemicals

  • L. Gayle Littlefield
  • Shirley P. Colyer
  • Anne M. Sayer
  • Russell J. DuFrain

Abstract

We conducted studies to determine whether cycling human lympho cytes are equally efficient in repairing sister chromatid exchange (SCE)-producing lesions induced by differing classes of DNA-damaging chemicals. Lymphocytes were pulse-treated during GO with mitomycin C (MMC), N,N′,N″-triethylenethiophosphoramide (ThioTEPA), ethyl-methanesulfonate (EMS), or cis-diamminedichloroplatinum (cis-DDP). Bromodeoxyuridine (BrdUrd) was added to the 72 hr cultures at 0 hr or at 48 hr after phytohemmagglutinin stimulation. The concentrations of chemicals employed induced a greater than 2-fold increase in SCEs in second-division metaphases from lymphocytes cultured in the presence of BrdUrd for the entire 72 hr. The analysis of SCEs in uniformly harlequinized metaphases from GO-treated lymphocytes cultured in BrdUrd for the terminal 24 hr showed no increase above baseline after exposure to MMC, and intermediate increases above baseline after exposures to ThioTEPA and cis-DDP. However, after GO treatment with EMS, the observed SCE frequency was consistent with that expected had all DNA lesions persisted and continued to give rise to SCEs during 3 cell cycles. These findings suggest that cycling human lymphocytes are not equally efficient in eliminating SCE-producing lesions after exposure to differing classes of DNA-damaging chemicals.

Keywords

Human Lymphocyte Sister Chromatid Exchange Sister Chromatid Exchange Frequency Entire Culture Period Bifunctional Alkylating Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    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
  2. 2.
    Stetka, D.G., and S. Wolff (1976) Sister chromatid exchange as an assay for genetic damage induced by mutagen-carcinogens. I. In vivo test for compounds requiring metabolic activation. Mutat. Res. 41:333–342.PubMedCrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    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
  5. 5.
    Lambert, B., R. Ulrik and A. Lindblad (1979) Prolonged in crease of sister-chromatid exchanges in lymphocytes of melanoma patients after CCNU treatment. Mutat. Res. 59:295–500.PubMedCrossRefGoogle Scholar
  6. 6.
    Lambert, B., U. Ringborg, E. Harper, and A. Lindblad (1978) Sister chromatic exchanges in lymphocyte cultures of patients receiving chemotherapy for malignant disorders. Cancer Treat ment Reports 62:1413–1419.Google Scholar
  7. 7.
    Ohtsuru, M., Y. Ishii, S. Taki, H. Higashi, and G. Kosaki (1980) Sister chromatid exchanges in lymphocytes of cancer patients receiving mitomycin C treatment. Cancer Res. 40:477–480.PubMedGoogle Scholar
  8. 8.
    Littlefield, L.G., S.P. Colyer, and R.J. DuFrain (1980) Comparison 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
  9. 9.
    Kram, D., G.D. Bynum, R. Dean, E.L. Schneider, W.H. Farland, and J.R. Williams (1981) Effects of acute and chronic administration of MMC on the induction of sister chromatid exchanges in vivo. Environ. Mutagen. 3:489–495.PubMedCrossRefGoogle Scholar
  10. 10.
    Kato, H. (1974) Induction of sister chromatid exchanges by chemical mutagens and its possible relevance to DNA repair. Exp. Cell Res. 85:239–247.PubMedCrossRefGoogle Scholar
  11. 11.
    Muscarella, D.E., and S.E. Bloom (1982) The longevity of chemically induced sister chromatid exchanges in Chinese hamster ovary cells. Environ. Mutagen. 4:467–475.CrossRefGoogle Scholar
  12. 12.
    Wolff, S. (1978) Chromosomal effects of mutagenic carcinogens and the nature of lesions leading to sister chromatid exchange. In Mutagen-Induced Chromosome Damage in Man, H.J. Evans and D.C. Lloyd eds. Yale University Press, New Haven, pp. 208–215.Google Scholar
  13. 13.
    Linnainmaa, K., and S. Wolff (1982) Sister chromatid exchange induced by short-lived monoadducts produced by the bifunctional agents mitomycin C and 8-Methoxypsoralen. Environ. Mutagen. 4: 239–247.PubMedCrossRefGoogle Scholar
  14. 14.
    Taylor, J.H. (1958) Sister chromatid exchanges in tritium-labeled chromosomes. Genetics 43:515–529.PubMedGoogle Scholar
  15. 15.
    Tice, R., J. Chaillet, and E.L. Schneider (1975) Evidence derived from sister chromatid exchanges of restricted rejoining of chromatid subunits. Nature (Lond.) 256:642–644.CrossRefGoogle Scholar
  16. 16.
    Ishii, Y., and M.A. Bender (1978) Factors affecting the frequency of mitomycin C-induced sister-chromatid exchanges in 5-bromodeoxyuridine-substituted human lymphocytes in culture. Mutat. Res. 51:411–418.PubMedCrossRefGoogle Scholar
  17. 17.
    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
  18. 18.
    Littlefield, L.G. (1982) Effects of DNA-damaging agents on SCE. In Sister Chromatid Exchange, A.A. Sandberg, ed. Alan R. Liss, Inc., New York, pp. 355–394.Google Scholar
  19. 19.
    Littlefield, L.G., S.P. Colyer, E.E. Joiner, and R.J. DuFrain (1979) Sister chromatid exchanges in human lymphocytes exposed to ionizing radiation during GO. Rad. Res. 78:514–521.CrossRefGoogle Scholar
  20. 20.
    Perry, P., and S. Wolff (1974) New Giemsa method for differen tial staining of sister chromatids. Nature (Lond.) 251:156–158.CrossRefGoogle Scholar
  21. 21.
    Wolff, S. (1981) Induced chromosome variation. Chromosomes Today 7:226–241.Google Scholar
  22. 22.
    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
  23. 23.
    Morrison, W.D., V. Huff, S.P. Colyer, R.J. DuFrain, and L.G. Littlefield (1981) Cytogenetic effects of cis-Platinum(II) Diamminedichloride in vivo. Environ. Mutagen. 3:265–274.PubMedCrossRefGoogle Scholar
  24. 24.
    Carrano, A.V., L.H. Thompson, D.G. Stetka, J.L. Minkler, J. A. Mazrimas, and S. Fong (1979). DNA crosslinking, sister-chromatid exchange and specific mutations. Mutat. Res. 63:175–188.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • L. Gayle Littlefield
    • 1
  • Shirley P. Colyer
    • 1
  • Anne M. Sayer
    • 1
  • Russell J. DuFrain
    • 1
  1. 1.Radiation Emergency Assistance Center/Training Site Medical and Health Sciences DivisionOak Ridge Associated UniversitiesOak RidgeUSA

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