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. 1989 Aug;29(4):303–306. doi: 10.1007/BF00199219

Increased bleomycin-induced chromosome damage in lymphocytes of patients with common variable immunodeficiency indicates an involvement of chromosomal instability in their cancer predisposition

Igor Vorechovsky 1,✉, Marta Munzarova 2, Jindrich Lokaj 3
PMCID: PMC11038777  PMID: 2473834

Abstract

To study mutagen-induced chromosome instability in cancer disposition, late S and G2 lymphocytes of 15 patients with common variable immunodeficiency and 14 healthy controls were exposed to bleomycin in vitro. The groups did not differ in the frequency of spontaneous chromosome aberrations. In bleomycin-treated samples we found higher numbers of break events per cell and increased frequency of cells with aberrations compared to the control group. A slightly reduced breakage of chromosome group D was noted in patients. These results support the hypothesis that a higher incidence of cancer in patients with genetically determined immunodeficiencies may be explained by an increased mutagen-induced chromosome instability in at least some of them.

Keywords: Cancer Research, Bleomycin, Chromosome Aberration, Chromosome Instability, Break Event

References

  • 1.Alalawi FA, Chapman IV. Combined effects of bleomycin and X-rays on DNA synthesis in asynchronous Ehrlich ascites cells in suspension. Br J Cancer. 1977;36:78–83. doi: 10.1038/bjc.1977.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Cherry LM, Hsu TC. Bleomycin-induced chromosome damage in lymphocytes of medullary thyroid carcinoma patients and their family members. Anticancer Res. 1983;3:367–372. [PubMed] [Google Scholar]
  • 3.Den Otter W. Tumor cells do not arise frequently. Cancer Immunol Immunother. 1985;19:159–162. doi: 10.1007/BF00199220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Den Otter W. Immune surveillance and natural resistance: an evaluation. Cancer Immunol Immunother. 1986;21:85–92. doi: 10.1007/BF00199854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Durham JC, Stephens DS, Rimland D, Nassar VH, Spira TJ. Common variable hypogammaglobulinemia complicated by an unusual T-suppressor/cytotoxic cell lymphoma. Cancer. 1987;59:271–276. doi: 10.1002/1097-0142(19870115)59:2<271::aid-cncr2820590216>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  • 6.Gantt R, Parshad R, Price FM, Sanford KK. Biochemical evidence for deficient DNA repair leading to enhanced G2 chromatid radiosensitivity and susceptibility to cancer. Radiat Res. 1987;108:117–126. [PubMed] [Google Scholar]
  • 7.German J. Chromosome mutation and neoplasia. New York: Alan R Liss; 1983. p. 452. [Google Scholar]
  • 8.Harnden DG, Klinger HP. An international system for human cytogenetic nomenclature (ISCN) New York: Karger; 1985. p. 66. [Google Scholar]
  • 9.Hsu TC. Genetic instability in the human population: a working hypothesis. Hereditas. 1983;98:1–9. doi: 10.1111/j.1601-5223.1983.tb00574.x. [DOI] [PubMed] [Google Scholar]
  • 10.Hsu TC. Genetic predisposition to cancer with special reference to mutagen sensitivity. In Vitro Cell Dev Biol. 1987;23:591–603. doi: 10.1007/BF02621067. [DOI] [PubMed] [Google Scholar]
  • 11.Hsu TC, Cherry LM, Samaan NA. Differential mutagen susceptibility in cultured lymphocytes of normal individuals and cancer patients. Cancer Genet Cytogenet. 1985;17:307–313. doi: 10.1016/0165-4608(85)90114-1. [DOI] [PubMed] [Google Scholar]
  • 12.Hultén M. Selective somatic pairing and fragility at 1q12 in a boy with common variable immunodeficiency. Clin Genet. 1978;14:294. [Google Scholar]
  • 13.Jaspers NGJ, Taalman RDFM, Baan C. Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia. Am J Hum Genet. 1988;42:66–73. [PMC free article] [PubMed] [Google Scholar]
  • 14.Kinlen LJ, Webster ADB, Bird AG, Haile R, Peto J, Soothill JF, Thompson RA. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet. 1985;i:263–266. doi: 10.1016/s0140-6736(85)91037-2. [DOI] [PubMed] [Google Scholar]
  • 15.Maraschio P, Zuffardi O, Fior TD, Tiepolo L. Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial abnormalities: the ICF syndrome. J Med Genet. 1988;25:173–180. doi: 10.1136/jmg.25.3.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Östling O, Johanson KJ. Bleomycin, in contrast to gamma irradiation, induces extreme variation of DNA strand breakage from cell to cell. Int J Radiat Biol. 1987;52:683–691. doi: 10.1080/09553008714552201. [DOI] [PubMed] [Google Scholar]
  • 17.Parshad R, Gantt R, Sanford KK, Jones GM, Tarone RE. Repair of chromosome damage induced by X-irradiation during G2 phase in a line of normal human fibroblasts and its malignant derivative. J Natl Cancer Inst. 1982;69:409–414. [PubMed] [Google Scholar]
  • 18.Parshad R, Sanford KK, Jones GM. Chromatid damage after G2 phase x-irradiation of cells from cancer-prone individuals implicates deficiency in DNA repair. Proc Natl Acad Sci USA. 1983;80:5612–5616. doi: 10.1073/pnas.80.18.5612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Parshad R, Gantt R, Sanford KK, Jones GM. Chromosomal radiosensitivity of human tumor cells during the G2 cell cycle period. Cancer Res. 1984;44:5577–5582. [PubMed] [Google Scholar]
  • 20.Penn I. Occurrence of cancer in immune deficiencies. Cancer. 1974;34:858–866. doi: 10.1002/1097-0142(197409)34:3+<858::aid-cncr2820340712>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  • 21.Seemanova E, Passarge E, Beneskova D, Houstek J, Kasal P, Sevcikova M. Familial microcephaly with normal intelligence, immunodeficiency, and risk for lymphoreticular malignancies: a new autosomal recessive disorder. Am J Med Genet. 1985;20:639–648. doi: 10.1002/ajmg.1320200410. [DOI] [PubMed] [Google Scholar]
  • 22.Spector BD, Perry GS, Kersey JH. Genetically determined immunodeficiency diseases (GDID) and malignancy: report from the Immunodeficiency-Cancer Registry. Clin Immunol Immunopathol. 1978;11:12–29. doi: 10.1016/0090-1229(78)90200-3. [DOI] [PubMed] [Google Scholar]
  • 23.Taalman RDFM, Weemaes CMR, Hustinx TWJ, Scheres JMJC, Clement JME, Stoelinga GBA. Chromosome studies in IgA-deficient patients. Clin Genet. 1987;32:81–87. doi: 10.1111/j.1399-0004.1987.tb03330.x. [DOI] [PubMed] [Google Scholar]
  • 24.Thomas L. On immunosurveillance in human cancer. Yale J Biol Med. 1982;55:329–333. [PMC free article] [PubMed] [Google Scholar]
  • 25.Valkova G, Ghenev E, Tzancheva M. Centromeric instability of chromosomes 1, 9 and 16 with variable immune deficiency. Support for a new syndrome. Clin Genet. 1987;31:119–124. doi: 10.1111/j.1399-0004.1987.tb02781.x. [DOI] [PubMed] [Google Scholar]
  • 26.Vorechovsky I, Zaloudik J (1989) Increased breakage of chromosome 1 in lymphocytes of patients with testicular cancer after bleomycin treatment in vitro. Brit J Cancer (in press) [DOI] [PMC free article] [PubMed]
  • 27.Wegner RD, Metzger M, Hanefeld F, Jaspers NGJ, Baan C, Magdorf K, Kunze J, Sperling K. A new chromosomal instability disorder confirmed by complementation studies. Clin Genet. 1988;33:20–32. [PubMed] [Google Scholar]

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