Skip to main content
Log in

Chromosome studies on lymphocytes of patients under cytostatic therapy

I. Conventional chromosome studies in cytostatic interval therapy

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

Chromosome studies were performed on lymphocyte cultures from the peripheral blood of 43 patients undergoing a cytostatic interval therapy with a regimen of methyl-CCNU, 5-fluorouracil, and vincristine. From a total of 229 individual examinations (30 prior to the start of therapy, the rest at different stages of the therapy) more than 23 000 metaphases were analysed for structural chromosome aberrations (i.e., gaps, breaks, and interchanges).

A distinct increase in the aberration rate over the level in controls (i.e., the same patients and other patients of the same group prior to the start of therapy) was observed at all phases of therapy in all patients under study. This increase was not only correlated with the number of therapy rounds, but was also dependent on the particular composition of the drug regimen applied at the different phases of therapy. Furthermore, even 4 weeks after 5-day courses of therapy the aberration rates, although lower than immediately after drug administration, clearly exceeded those of controls in most cases. There was no distinct quantitative difference, but there was a clear qualitative difference between data gained from 48-h cultures and those obtained after 72-h lymphocyte cultures. A rather high interindividual variability of aberration rates and spectra was established in different patients at the same phases of therapy.

From these results the conclusion was drawn that chromosome studies in patients exposed to mutagenic chemicals are a suitable and reliable method of gaining insight into the clastogenicity of these substances in man (i.e., under the real conditions present in the human organism), if all the limitations of this method are seriously borne in mind.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

methyl-CCNU:

1-[2-chloroethyl-3-(4-methylcyclohexyl)]-1-nitrosourea

FU:

5-fluorouracil

VC:

vincristine

References

  • Arrighi, F. E., Hsu, T. C., Bergsagel, D. E.: Chromosome damage in murine and human cells following cytoxan therapy. Tex. Rep. Biol. Med. 20, 545–549 (1962)

    Google Scholar 

  • Bauchinger, M., Schmid, E.: Cytogenetische Veränderungen in weißen Blutzellen nach Cyclophosphamidtherapie. Z. Krebsforsch. 72, 77–87 (1969)

    Google Scholar 

  • Bempong, M. A., Trower, E. C.: Cytogenetic and biochemical effects of 5-fluorouracil in rats. Mutat. Res. 31, 303–304 (1975)

    Google Scholar 

  • Bornstein, R. S., Hungerford, D. A., Haller, G., Engstrom, P. F., Yarbro, J. W.: Cytogenetic effects of bleomycin therapy in man. Cancer Res. 31, 2004–2007 (1971)

    Google Scholar 

  • Brøgger, A.: Chromosome damage in man in human mitotic cells after in vivo and in vitro exposure to mutagens. In: Genetic damage in man caused by environmental agents, Berg, K. (ed.. New York, San Francisco, London: Academic Press 1979

    Google Scholar 

  • Conen, P. E., Lansky, G. S.: Chromosome damage during nitrogen mustard therapy. Br. Med. J. 1961 II, 1055–1057

    Google Scholar 

  • Dobos, M., Schuler, D., Fekete, G.: Cyclophosphamide-induced chromosomal aberrations in nontumorous patients. Humangenetik 22, 221–227 (1974)

    Google Scholar 

  • Forni, A., Secchi, G.: Chromosome changes in preclinical and clinical lead poisoning and correlation with biochemical findings. Paper presented at the International Symposium on Environmental Health Aspects of Lead, Amsterdam, 1972

  • Gebhart, E.: The treatment of human chromosomes in vitro: Results. In: Chemical mutagenesis in mammals and man. Vogel, F., Röhrborn, G. (eds.). Berlin, Heidelberg, New York: Springer 1970

    Google Scholar 

  • Gebhart, E.: Chromosomenaberrationen bei chemisch belasteten Patienten. Ärztl. Praxis 25, 665–666 (1973)

    Google Scholar 

  • Gebhart, E., Schwanitz, G., Hartwich, G.: Zytogenetische Wirkung von Vincristin auf menschliche Leukozyten in vivo und in vitro. Med. Klin. 51, 2366–2371 (1969)

    Google Scholar 

  • Gebhart, E., Schwanitz, G., Hartwich, G.: Chromosomenaberrationen bei Busulfan-Behandlung. Dtsch. Med. Wochenschr. 99, 52–56 (1974)

    Google Scholar 

  • Hampel, K. E.: Über die Wirkung von Zytostatika auf die Chromosomen des Menschen. Int. J. Clin. Pharmacol. 1, 322–371 (1968)

    Google Scholar 

  • Harrod, E. K., Cortner, J. A.: Prolonged survival of lymphocytes with chromosomal defects in children treated with 1,3-bis(2-chloroethyl)-1-nitrosourea. J. Natl. Cancer Inst. 40, 269–279 (1968)

    Google Scholar 

  • Kilian, D. J., Picciano, D.: Cytogenetic surveillance of industrial populations. In: Chemical mutagens, Vol. IV. Hollaender, A. (ed.). New York, London: Plenum 1976

    Google Scholar 

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

    Google Scholar 

  • Müller, D., Arni, H., Langauer, M., Strasser, F. F.: Comparative studies of 14 mutagenic or carcinogenic substances in seven mutagenicity test systems (point mutation tests, cytogenetic test and the dominant lethal test). Mutat. Res. 53, Abstract 148 (1978)

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

    Google Scholar 

  • Nielsen, J., Friedrich, U., Tsuboi, T.: Chromosome abnormalities in patients treated with chlorpromazine, perphenazine, and lysergide. Br. Med. J. 1969 III, 634–636

  • Purchase, I. F. H., Richardson, C. R., Anderson, D., Paddle, G. M., Adams, E. G. F.: Chromosomal analyses in vinyl chloride-exposed workers. Mutat. Res. 57, 325–334 (1978)

    Google Scholar 

  • Raposa, T.: Sister chromated 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)

    Google Scholar 

  • Schinzel, A., Schmid, W.: Lymphocyte chromosome studies in humans exposed to chemical mutagens: The validity of the method in 67 patients under cytostatic therapy. Mutat. Res. 40, 139–166 (1976)

    Google Scholar 

  • Selezneva, T. G., Korman, N. P.: Study of lymphocyte chromosomes from patients treated with N-nitroso-N-methylurea. Genetika 8, 181–183 (1972)

    Google Scholar 

  • Sokova, O. I., Volgareva, G. M.: The effect of ftuorafur and 5-fluorouracil on chromosomes of normal and tumor cells in vivo. Vopr. Onkol. 23, 94–97 (1977)

    Google Scholar 

  • Sokova, O. I., Volgareva, G. M.: Effect of ftuorafur and 5-fluorouracil on the chromosomes of human tumour cells in vitro. Genetika 15, 855–861 (1979)

    Google Scholar 

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

    Google Scholar 

  • Tates, A. D., Natarajan, A. T.: A correlative study on the genetic damage induced by chemical mutagens in bone marrow and spermatogonia of mice. I. CNU-ethanol. Mutat. Res. 37, 267–278 (1976)

    Google Scholar 

  • Tates, A. D., Natarajan, A. T., De Vogel, N., Meijers, M.: A correlative study on the genetic damage induced by chemical mutagens in bone marrow and spermatogonia of mice. III. 1,3-bis(2-chloroethyl)-3-nitrosourea (BCNU). Mutat. Res. 44, 87–95 (1977)

    Google Scholar 

  • Van Bao, T., Szabo, I., Ruzicska, P., Czeizel, A.: Chromosome aberrations in patients suffering acute organic phosphate insecticide intoxication. Humangenetik 24, 33–57 (1974)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dedicated to Prof. Dr. A. Barthelmeß on the occasion of his 70th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gebhart, E., Lösing, L. & Wopfner, F. Chromosome studies on lymphocytes of patients under cytostatic therapy. Hum. Genet. 55, 53–63 (1980). https://doi.org/10.1007/BF00329127

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00329127

Keywords

Navigation