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.
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References
Bartram CR, Mortier W, Schmidt A (1981) Human fibroblast interferon does not induce chromosomal abnormalities. Lancet I:1372
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
De Braekeleer M, Smith B, Lin CC (1985) Fragile sites and structural rearrangements in cancer. Hum Genet 69:112–116
Friedman RL, Stark GR (1985) Alpha interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature 314:637–639
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
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
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
Hecht F, Sutherland GR (1984) Fragile sites and cancer breakpoints. Cancer Genet Cytogenet 12:179–181
Hecht F, Kaiser-McCaw B, Jacky PB (1981) Interferon-inducible fragile site on chromosome 16. Lancet I:108
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
Kirkova ZS, Shvetzova TP, Zasukhina GD (1980) Suppressive effect of interferon on the occurrence of chromosome aberrations. Hereditas 93:165–168
Le Beau MM, Rowley JD (1984) Heritable fragile sites in cancer. Nature 308:607–608
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
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
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
Meisner LF, Gilbert E, Ris HW, Haverty G (1979) Genetic mechanisms in cancer predisposition. Report of a cancer family. Cancer 43:679–689
Scott JA (1982) On the biochemical similarities of ascorbic acid and interferon. J Theor Biol 98:235–238
Shabtai F, Bichacho S, Halbrecht I (1980) The fragile site on chromosome 16 (q21q22). Data on four new families. Hum Genet 55:19–22
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
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
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
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
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
Sørensen PJ, Jensen MK, Jersild C (1981) Effect of human leukocyte interferon on human lymphocytes in vitro: cytogenetic studies. Mutat Res 90:143–147
Sutherland GR (1979) Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culture. Am J Hum Genet 31:125–135
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
Tyrrell DAJ (1981) Research on interferon: a review. J R Soc Med 74:145–146
Vijayalaxmi (1982) Human leukocyte interferon does not induce sister-chromatid exchanges in human blood lymphocytes. Mutat Res 105:287–290
Yunis JJ (1984) Fragile sites and predisposition to leukemia and lymphoma. Cancer Genet Cytogenet 12:85–88
Yunis JJ, Soreng AL (1984) Constitutive fragile sites and cancer. Science 226:1199–1204
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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
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DOI: https://doi.org/10.1007/BF00273838