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Chromosome studies on lymphocytes of patients under cytostatic therapy

II. Studies using the BUDR-labelling technique in cytostatic interval therapy

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Summary

Lymphocyte cultures from the peripheral blood of 38 patients undergoing a cytostatic interval therapy with a regimen of methyl-CCNU (1-[2-chloroethyl-3-(4-methyl-cyclohexyl)]-1-nitrosourea), 5-fluorouracil, and vincristine (each 5-day course of therapy was followed by a therapy interval of 4 weeks) were supplied with 5-bromodeoxyuridine (BUDR) for the whole culture time to determine the sister chromatid labelling pattern. From a total of 92 individual blood samples sister chromatid exchange (SCE) studies were performed including analyses before the start of the therapy, and immediately and 4 weeks after each course of therapy. In addition, the frequency of first, second, and third metaphases in the 72-h cultures was estimated using the characteristic labelling patterns.

A distinct increase of SCE frequency over the control level (i.e., lymphocyte cultures of patients before the start of therapy) was observed at all phases of therapy. It was clearly correlated with the number of courses of therapy up to course 7, later on the SCE rate remained more or less at the level reached. The influence of the composition of each drug regimen on the SCE rate was less pronounced than it was on the breakage rate. Moreover, although a clear correlation existed between the individual rates of breakage and SCE, the formation of the latter appeared to reflect a long-term effect of the therapy rather than did the formation of break aberrations. In addition, as the intercellular variability of the number of SCEs per cell was much higher than that of breaks, the interindividual variability (variation of the mean values for each patient) was small compared to the respective variability of breakage rates.

The proportion of first, second, and third metaphases present in 72-h cultures evidently was influenced by single courses of therapy. The observed delay of proliferation was also reflected in different amounts of chromosome damage. Although the BUDR treatment enhanced the cytostatic effect of the therapy on the lymphocytes in culture rendering SCE analysis rather difficult in several cases, the other data of this study and in particular the experiences with the “long-term effect” make it imperative to include BUDR-labelling in further cytogenetic studies in subjects with exceptional exposure to chemicals. However, the SCE method can by no means, replace the classic cytogenetic analysis.

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References

  1. Abe S, Sasaki M (1977) Chromosome aberrations and sister chromatid exchanges in Chinese hamster cells exposed to various chemicals. J Natl Cancer Inst 58:1635–1640

  2. Bauknecht T, Vogel W, Bayer U, Wild D (1977) Comparative in vivo mutagenicity testing by SCE and micronucleus induction in mouse bone marrow. Hum Genet 35:299–307

  3. Beek B, Obe G (1975) The human leukocyte test system. IV The use of sister chromatid exchanges as a possible indicator for mutagenic activities. Humangenetik 29:127–134

  4. Burgdorf W, Kurvink K, Cervenka J (1977) Elevated sister chromatid exchange rate in lymphocytes of subjects treated with arsenic. Hum Genet 36:69–72

  5. Chaganti RSK, Schonberg S, German J (1974) A many-fold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. Proc Natl Acad Sci USA 71:4508–4512

  6. Crossen PE, Drets ME, Arrighi FE, Johnston DA (1977) Analysis of the frequency and distribution of sister chromatid exchanges in cultured human lymphocytes. Hum Genet 35:345–352

  7. Crossen PE, Morgan WF (1977) Analysis of human lymphocyte cell cycle time in culture measured by sister chromatid differential staining. Exp Cell Res 104:453–457

  8. Crossen PE, Morgan WF (1977) Proliferation of PHA- and PWM-stimulated lymphocytes measured by sister chromatid differential staining. Cell Immunol 32:432–438

  9. Daoud C, Shaw MW, Craig-Holmes A (1976) Sister chromatid exchange frequency among normal individuals and breast cancer patients. Mamm Chrom Newsl 17:26

  10. Evans HJ (1977) What are sister chromatid exchanges? In: De La Chapelle A, Sorsa M (eds) Chromosomes today. Amsterdam New York Oxford, p 316

  11. Galloway SM (1977) What are sister chromatid exchanges? In: Nichols WW, Murphy DG (eds) DNA repair processes. Miami, p 191

  12. Gebhart E, Kappauf H (1978) Bleomycin and sister-chromatid exchange in human lymphocyte chromosomes. Mutat Res 58:121–124

  13. Gebhart E, Kappauf H (1980) The action of three anticlastogens on the induction of sister chromatid exchange by Trenimon and 8-hydroxyquinoline sulfate in human lymphocyte cultures. Environ Mutagen 2:191–200

  14. Gebhart E, Lösing J, Wopfner F (1980) Chromosome studies on lymphocytes of patients under cytostatic therapy. I Conventional chromosome studies in cytostatic interval therapy. Hum Genet 55:53–63

  15. Hayashi K, Schmid W (1975) The rate of sister chromatid exchanges parallel to spontaneous breakage in Fanconi's anemia and to Trenimon-induced aberrations in human lymphocytes and fibroblasts. Humangenetik 29:201–206

  16. Kato H (1974) Induction of sister chromatid exchanges by chemical mutagens and its possible relevance to DNA repair. Exp Cell Res 85:239–247

  17. Korenberg JR, Freedlender EF (1974) Giemsa technique for the detection of sister chromatid exchanges. Chromosoma 48:355–360

  18. Lambert B, Ringborg U, Harper E, Lindblad A (1978) Sister chromatid exchanges in lymphocyte cultures of patients receiving chemotherapy for malignant disorders. Cancer Treat Rep 62:1413–1419

  19. Latt SA (1974) 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

  20. Morgan WF, Crossen PE (1977) The incidence of sister chromatid exchanges in cultures human lymphocytes. Mutat Res 42:305–312

  21. Morgan WF, Crossen PE (1980) Mitotic spindle inhibitors and sister chromatid exchange in human chromosomes. Mutat Res 77:283–286

  22. Musilova J, Michalova K, Urban J (1979) Sister chromatid exchanges and chromosomal breakage in patients treated with cytostatics. Mutat Res 67:289–294

  23. Perry P, Wolff S (1974) New Giemsa method for the differential staining of sister chromatids. Nature 251:156–158

  24. Perry P, Evans HJ (1975) Cytological detection of mutagencarcinogen exposure by sister chromatid exchanges. Nature 258:121–125

  25. Popescu NO, Turnbull D, Di Paolo JA (1977) Sister chromatid exchange and chromosome aberration analysis with the use of several carcinogens and noncarcinogens. J Natl Cancer Inst 59:289–292

  26. Raposa T (1978) 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

  27. Renner HW (1979) Zur Bewertung des In-vivo-SCE (sisterchromatid-exchange)-Tests, dargestellt an verschiedenen Zytostatika. Arzneim-Forsch 29:1871–1875

  28. Shiraishi Y, Sandberg AA (1979) 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 62:27–35

  29. Solomon E, Bobrow M (1975) Sister chromatid exchange—a sensitive assay of agents damaging human chromosomes. Mutat Res 30:273–278

  30. Sono A, Sakaguchi K (1978) Induction of sister chromatid exchanges in Chinese hamster cells by antitumor agents and its relation to chromosome aberrations. Cell Struct Funct 3:341–347

  31. Stetka DG, Wolff S (1976) Sister chromatid exchanges as an assay for genetic damage induced by mutagens-carcinogens I and II. Mutat Res 41:333–350

  32. Stoll C, Borgaonkar DS, Levy JM (1976) Effect of vincristine on sister chromatid exchanges of normal human lymphocytes. Cancer Res 36:2710–2713

  33. Vogel W, Bauknecht T (1976) Differential chromatid staining by in vivo treatment as a mutagenicity test system. Nature 260:448–449

  34. Wolff S (1979) Sister chromatid exchange: The most sensitive mammalian system for determining the effects of mutagenic carcinogens. In: Berg K (ed) Genetic damage in man caused by environmental agents. Academic Press, New York San Francisco London, p 229

  35. Wolff S, Carrano AV (1979) Report of the workshop on the utility of sister-chromatid exchange. Mutat Res 64:53–56

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Correspondence to E. Gebhart.

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Gebhart, E., Windolph, B. & Wopfner, F. Chromosome studies on lymphocytes of patients under cytostatic therapy. Hum Genet 56, 157–167 (1980). https://doi.org/10.1007/BF00295688

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Keywords

  • Sister Chromatid Exchange
  • Labelling Pattern
  • Lymphocyte Culture
  • Nitrosourea
  • Characteristic Labelling