Advertisement

Practical Applications of the SCE Studies for Guiding and Improving Chemotherapy

  • A. Kourakis
  • J. Dozi-Vassiliades
  • P. Hatzitheodoridou
  • J. Tsiouris
  • D. Mourelatos

Abstract

The effect of diphylline (DP) or (1,2-dihydroxy-3-propyl)-theophylline and theobromine (TB) on sister chromatid exchange (SCE) rates induced in vitro by cytosine arabinoside (AraC) was studied in normal human lymphocytes. The combined treatments with AraC plus DP or TB showed the potentiating ability of the latter drugs.

In a combined in vivo and in vitro study, lymphocytes taken from 14 patients suffering from various types of cancer who had been given Cytoxan (5 patients) or AraC (9 patients) by injection 3 hr before and then treated with DP or TB in vitro were found to have synergistically increased exchange rates. This has implications for interpreting the repair processes involved and for monitoring drug combinations that synergistically damage DNA in vivo and in vitro.

Keywords

Chronic Lymphocytic Leukemia Human Lymphocyte Alkylating Agent Sister Chromatid Exchange Cytosine Arabinoside 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Perry, P., and H.J. Evans (1975) Cytological detection of muta gen carcinogen exposure by SCE. Nature (Lond.) 258:121–125.PubMedCrossRefGoogle Scholar
  2. 2.
    Nevstad, N.P. (1978) SCEs and chromosome aberrations induced in human lymphocytes by the cytostatic drug adriamycin in vivo and in vitro. Mutat. Res. 57:253–258.PubMedCrossRefGoogle Scholar
  3. 3.
    Ohtsuru, M., Y. Ishii, S. Takai, S. Higashi, and G. Kosaki (1980) SCEs in lymphocytes of cancer patients receiving MMC treatment. Cancer Res. 40:477–480.PubMedGoogle Scholar
  4. 4.
    Raposa, T. (1981) Some practical applications of the SCE studies in human leukemic patients. Mutat. Res. 85:239–240.Google Scholar
  5. 5.
    Faed, M.J.W., and D. Mourelatos (1978) Enhancement by caffeine of SCE frequency in lymphocytes from normal subjects after treatment by mutagens. Mutat. Res. 49:437–440.PubMedCrossRefGoogle Scholar
  6. 6.
    Vshii, Y., and M. Bender (1978) Caffeine inhibition of prereplication repair of MMC-induced DNA damage in human lymphocytes. Mutat. Res. 51:419–425.CrossRefGoogle Scholar
  7. 7.
    Mourelatos, D. (1979) Enhancement by caffeine of SCE frequency induced by antineoplastic agents in human lymphocytes. Exper ientia 35:822–824.CrossRefGoogle Scholar
  8. 8.
    Mourelatos, D., J. Dozi-Vassiliades, and A. Granitsas (1982) Antitumor alkylating agents act synergistically with methlyxanthines on induction of SCEs in human lymphocytes. Mutat. Res.104:243–247.PubMedCrossRefGoogle Scholar
  9. 9.
    Perry, P., and S. Wolf (1974) New Giemsa method for the differential staining of sister chromatids. Nature (Lond.) 251:156–158.CrossRefGoogle Scholar
  10. 10.
    Raposa, T. (1978) SCE-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.PubMedCrossRefGoogle Scholar
  11. 11.
    Beek, B., and G. Obe (1974) The human lymphocyte test system. II. Different sensitivities of subpopulations to a chemical mutagen. Mutat. Res. 24:395–398.PubMedCrossRefGoogle Scholar
  12. 12.
    Morgan, W.F., and J.E. Cleaver (1982) 3-Aminobenzamide synergistically increases SCEs in cells exposed to methylmethanesul-fonate but not to ultraviolet light. Mutat. Res. 104:361–366.PubMedCrossRefGoogle Scholar
  13. 13.
    Purnell, M., and W. Whish (1980) Novel inhibitors of poly(ADP-ribose)synthetase. Bioc hem. J. 185:775–777.Google Scholar
  14. 14.
    Durkacz, B., O. Omidiji, D. Gray, and S. Shall (1980) (ADP-ribose) participates in DNA excision repair. Nature (Lond.) 283:593–n596.CrossRefGoogle Scholar
  15. 15.
    Byfield, J.E., J. Murnane, J.E. Ward, P. Calabro-Jones, M. Lynch, and F. Kulhanian (1981) Mice, man, mustards and methylated xanthines: The potential role of caffeine and related drugs in the sensitization of human tumours to alkylating agents. Br. J. Cancer 43:669–683.PubMedCrossRefGoogle Scholar
  16. 16.
    Gaudin, D., K.L. Yieldin, A. Stabler, and G. Brown (1971) The effect of DNA repair inhibitors on the response of tumours treated with X-ray and alkylating agents. Proc. Soc. Exp.Biol. Med. 137:202–206.PubMedGoogle Scholar
  17. 17.
    Nomura, T. (1976) Diminution of tumorigenesis initiated by 4-NQO by post-treatment with caffeine. Nature (Lond.) 260:547–549.CrossRefGoogle Scholar
  18. 18.
    Cohen, M.H. (1972) Enhancement of antitumour effect of 1,3-bis-(2-chloroethyl)-l-nitrosourea by vitamin A and caffeine. J. Natl. Cancer Inst. 48:927–932.PubMedGoogle Scholar
  19. 19.
    Mourelatos, D., J. Dozi-Vassiliades, V. Tsigalidou-Balla, and A. Granitsas (1983) Enhancement by methylxanthines of SCE fre quency induced by cytostatics in normal and leukemic human lymphocytes. Mutat. Res. 121:147–152.PubMedCrossRefGoogle Scholar
  20. 20.
    Huang, A.T. (1975) Increased excision DNA repair as pathogenesis of a Human Leukemia. In Molecular Mechanisms for Repair of DNA, P. Hanawalt and R.B. Setlow, eds. Plenum Publishing Corporation, New York, pp. 805–806.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • A. Kourakis
    • 1
  • J. Dozi-Vassiliades
    • 1
  • P. Hatzitheodoridou
    • 1
  • J. Tsiouris
    • 2
  • D. Mourelatos
    • 3
  1. 1.Department of General Biology, Faculty of MedicineAristotelian UniversityThessalonikiGreece
  2. 2.Pediatric ClinicSaint Sophia University HospitalThessalonikiGreece
  3. 3.International Sister Chromatid Exchange SymposiumGreece

Personalised recommendations