Skip to main content

Advertisement

Log in

Alpha-interferon and fragility at 16q22

A study on 15 selected controls and 146 selected patients

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

Summary

Inducibility or enhancement of fragility at 16q22 by alpha-interferon has been found in a Danish laboratory and in our laboratory. Several other studies were not able to confirm these findings. We present the results of a large study on peripheral blood lymphocytes of 15 selected controls and 146 selected patients treated in vitro by alpha-interferon. In some of our patients parallel studies with distamycin A were performed. Both interferon and distamycin A induced the same fragility, but only in some patients. Both agents were not consistently able to enhance a spontaneously expressed 16q22 fragility. 16q22 is the location of the metallothionein genes, whose transcription is induced by interferon. The induction of the metallothionein gene transcription and the 16q22 fragility, however, do not seem to be directly related. To explain our findings we advance the hypothesis that fragility at 16q22 may be a modification induced by virus(es) with selective tropism for cells which are differently influenced by a pleiotropic action of interferon.

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

References

  • Bartram CR, Mortier W, Schmidt A (1981) Human fibroblast interferon does not induce chromosomal abnormalities. Lancet I:1372

    Google Scholar 

  • Bisballe S, Thestrup-Pedersen K, Bjerring P, Jensen JJ, Ottosen PD, Kaltoft K (1984) Eosinophilic granuloma associated with a 16q22 chromosomal defect of cutaneous T lymphocytes. Acta Derm Venereol (Stockh) 64:548–551

    Google Scholar 

  • De Braekeleer M, Smith B, Lin CC (1985) Fragile sites and structural rearrangements in cancer. Hum Genet 69:112–116

    Google Scholar 

  • Friedman RL, Stark GR (1985) Alpha interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature 314:637–639

    Google Scholar 

  • Fuhlbrigge RC, Edwards BS, Borden EC (1984) Effects of alpha-interferon on the sheep erythrocyte “receptor” of human lymphocytes. J Interferon Res 4:499–505

    Google Scholar 

  • Haas OA, Nacheva E, Schwarzmeier JD (1985) Noninvolvement of chromosome 16 in karyotype evolution of acute myeloid leukemia in a patient with a heritable fragile site. Cancer Genet Cytogenet 17:1–12

    Google Scholar 

  • Haslinger A, Karin M (1985) Upstream promotor element of the human metallothionein IIA gene can act like an enhancer element. Proc Natl Acad Sci USA 82:8572–8576

    Google Scholar 

  • Hecht F, Sutherland GR (1984) Fragile sites and cancer breakpoints. Cancer Genet Cytogenet 12:179–181

    Google Scholar 

  • Hecht F, Kaiser-McCaw B, Jacky PB (1981) Interferon-inducible fragile site on chromosome 16. Lancet I:108

    Google Scholar 

  • Karin M, Eddy RL, Henry WM, Haley LL, Byers MG, Shows TB (1984) Human metallothionein genes are clustered on chromosome 16. Proc Natl Acad Sci USA 81:5494–5498

    Google Scholar 

  • Kirkova ZS, Shvetzova TP, Zasukhina GD (1980) Suppressive effect of interferon on the occurrence of chromosome aberrations. Hereditas 93:165–168

    Google Scholar 

  • Le Beau MM, Rowley JD (1984) Heritable fragile sites in cancer. Nature 308:607–608

    Google Scholar 

  • Le Beau MM, Larson RA, Bitter MA, Vardiman GW, Golomb HM, Rowley JD (1983) Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association. N Engl J Med 309:630–636

    Google Scholar 

  • Le Beau MM, Diaz MO, Karin M, Rowley JD (1985) Metallothionein gene cluster is split by chromosome 16 rearrangements in myelomonocytic leukemia. Nature 313:709–711

    Google Scholar 

  • Matheson DS, Green B, Tan YH (1981) Human interferon α and β inhibit T-cell-dependent and stimulate T-cell-independent mitogenesis and natural cytoxicity: relation to chromosome 21. Cell Immunol 65:366–372

    Google Scholar 

  • Meisner LF, Gilbert E, Ris HW, Haverty G (1979) Genetic mechanisms in cancer predisposition. Report of a cancer family. Cancer 43:679–689

    Google Scholar 

  • Scott JA (1982) On the biochemical similarities of ascorbic acid and interferon. J Theor Biol 98:235–238

    Google Scholar 

  • Shabtai F, Bichacho S, Halbrecht I (1980) The fragile site on chromosome 16 (q21q22). Data on four new families. Hum Genet 55:19–22

    Google Scholar 

  • Shabtai F, Klar D, Bichacho S, Hart J, Halbrecht I (1983a) Familial fragility on chromosome 16 (fra 16q22) enhanced by both interferon and distamycin A. Hum Genet 63:341–344

    Google Scholar 

  • Shabtai F, Klar D, Schwartz A, Moroz A, Halbrecht I (1983b) Marker chromosomes in a family with high incidence of cancer. Cancer Genet Cytogenet 9:281–287

    Google Scholar 

  • Shabtai F, Klar D, Kimchi D, Antebi E, Hart J, Halbrecht I (1984) Juxta-centromeric fragility of chromosomes 1, 2, 9, 16, and immunodeficiency. Special reference to the fragility of chromosome 2 and its oncogenic potential. Anticancer Res 4:235–240

    Google Scholar 

  • Shabtai F, Klar D, Hart J, Halbrecht I (1985) On the meaning of fragile sites in cancer risk and development. Cancer Genet Cytogenet 18:81–85

    Google Scholar 

  • Shabtai F, Orlin J, Hart J, Halbrecht I, Klar D, Friedman J (1986) Different inducibility and possible significance of several concomitant “fragile sites” in two brothers. Hum Genet 74:85–89

    Google Scholar 

  • Sørensen PJ, Jensen MK, Jersild C (1981) Effect of human leukocyte interferon on human lymphocytes in vitro: cytogenetic studies. Mutat Res 90:143–147

    Google Scholar 

  • Sutherland GR (1979) Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culture. Am J Hum Genet 31:125–135

    Google Scholar 

  • Thestrup-Pedersen K, Esmann V, Jensen JR, Hastrup J, Thorling K, Saemundsen AK, Bisballe S, Pallesen G, Madsen M, Masucci MG, Ernberg I (1980) Epstein-Barr-virus-induced lymphoproliferative disorder converting to fatal Burkitt-like lymphoma in a boy with interferon-inducible chromosomal defect. Lancet II:997–1002

    Google Scholar 

  • Tyrrell DAJ (1981) Research on interferon: a review. J R Soc Med 74:145–146

    Google Scholar 

  • Vijayalaxmi (1982) Human leukocyte interferon does not induce sister-chromatid exchanges in human blood lymphocytes. Mutat Res 105:287–290

    Google Scholar 

  • Yunis JJ (1984) Fragile sites and predisposition to leukemia and lymphoma. Cancer Genet Cytogenet 12:85–88

    Google Scholar 

  • Yunis JJ, Soreng AL (1984) Constitutive fragile sites and cancer. Science 226:1199–1204

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shabtai, F., Orlyn, J., Hart, J. et al. Alpha-interferon and fragility at 16q22. Hum Genet 75, 48–52 (1987). https://doi.org/10.1007/BF00273838

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00273838

Keywords

Navigation