Summary
The effect of the oligopeptide antibiotic distamycin A on human lymphocyte cultures was examined. Distamycin A specifically inhibits the condensation of the Y heterochromatin and induces a fragile site in the chromosome 16 (band q22) in some individuals. The optimal culture conditions under which an undercondensation of the Y heterochromatin and an induction of the fragile site in 16q22 can be achieved by in vitro treatment of lymphocytes were determined. This also permits the use of distamycin A in routine diagnostics of human chromosomes. The use of this technique in the analysis of translocations involving the Y chromosome is presented. The distamycin A-DNA interaction and the different possible explanations for the distamycin A-induced undercondensations of the Y heterochromatin and fragile sites 16q22 are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Caspersson T, Zech L, Johannsson C, Modest EJ (1970) Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma 30:215–227
Dutrillaux B (1977) New chromosome techniques. In: Yunis JJ (ed) Chromosomes in biology and medicine. Molecular structure of human chromosomes. Academic Press, New York San Francisco London, pp 233–265
Dutrillaux B, Lejeune J (1971) Sur une nouvelle technique d'analyse du caryotype humain. C R Seances Acad Sci 272:2638–2640
Funderburk SJ, Klisak I, Sparkes RS, Carrel RE (1982) Familial Y-autosome translocation in two unrelated girls. Ann Génét (Paris) 25:119–122
Hahn FE (1975) Distamycin A and netropsin. In: Corcoran JW, Hahn FE (eds) Antibotics. Vol III. Springer, Berlin Heidelberg New York, pp 79–100
Hecht F, Kaiser-McCaw B (1979) The importance of being a fragile site. Am J Hum Genet 31:223–225
Hecht Th, Cooke HJ, Cerillo M, Meer B, Reck G, Hameister H (1980) A new case of Y to X translocation in a female. Hum Genet 54:303–307
Hilwig I, Gropp A (1973) Decondensation of constitutive heterochromatin in L cell chromosomes by a benzimidazole compound (“33258 Hoechst”). Exp Cell Res 81:474–477
Hungerford DA (1971) Chromosome structure and function in man. I. Pachytene mapping in the male improved methods and a general discussion of initial results. Cytogenet Cell Genet 10: 23–32
Hungerford DA (1981) The fragile site at 16q22, distamycin A, and the normal pachytene structure of chromosome 16: some possible interrelationships. Cytogenet Cell Genet 30:63–64
Hungerford DA, Hungerford AM (1978) Chromosome structure and function in man. VI. Pachytene chromomere maps of 16, 17 and 18; pachytene as a reference standard for metaphase banding. Cytogenet Cell Genet 21:212–230
ISCN (1978) An international system for human cytogenetic nomenclature. Cytogenet Cell Genet 21:1–92
ISCN (1981) An international system for human cytogenetic nomenclature—high resolution banding. Cytogenet Cell Genet 31:1–23
Jotterand-Bellomo M (1983) Les effets de la distamycine A sur les cellules du liquide amniotique cultivees in vitro. Ann Génét (Paris) 26:27–30
Krey AK (1980) Non-intercalative binding to DNA. In: Hahn FE, Kersten H, Kersten W, Szybalski W (eds) Progress in molecular and subcellular biology. Vol 7. Springer, Berlin Heidelberg New York, pp 43–87
Kucherlapatti RS, Hilwig I, Gropp A, Ruddle FH (1975) Mammalian chromosome identification in interspecific hybrid cells using “Hoechst 33258”. Hum Genet 27:9–14
Magenis E, Chamberlin J (1979) Location of fragile site: 16q22.00. Cytogenet Cell Genet 25:180
Magenis RE, Hecht F, Lovrien EW (1970) Heritable fragile site on chromosome 16: probable localization of haptoglobin locus in man. Science 170:85–87
Marcus M, Goitein R, Gropp A (1979a) Condensation of all human chromosomes in phase G2 and early mitosis can be drastically inhibited by 33258 Hoechst treatment. Hum Genet 51:99–105
Marcus M, Nattenberg A, Goitein R, Nielsén K, Gropp A (1979b) Inhibition of condensation of human Y chromosome by the fluorochrome Hoechst 33258 in a mouse-human cell hybrid. Hum Genet 46:193–198
Martindale W (1977) The extrapharmacopeia. Incorporating Squire's companion, 27th edn. Pharmaceutical Press, London, p 1572
Page BM (1973) Identification of chromosome 9 in human male meiosis. Cytogenet Cell Genet 12:254–263
Prantera G, Pimpinelli S, Rocchi A (1979) Effects of distamycin A on human leukocytes in vitro. Cytogenet Cell Genet 23:103–107
Razavi L (1965) An inexpensive and simple method for preparing chromosome spreads. Proc Soc Exp Biol Med 118:717–719
Schmid M (1979) Demonstration of Y/autosomal translocations using distamycin A. Hum Genet 53:107–109
Schmid M, Klett C, Niederhofer A (1980) Demonstration of a heritable fragile site in human chromosome 16 with distamycin A. Cytogenet Cell Genet 28:87–94
Schmid M, Gall H, Schempp W, Weber L, Schmidtke J (1981a) Characterization of a new aberration of the human Y chromosome by banding methods and DNA restriction endonuclease analysis. Hum Genet 59:26–35
Schmid M, Poppen A, Engel W (1981b) The effects of distamycin A on gorilla, chimpanzee, and orangutan lymphocyte cultures. Cytogenet Cell Genet 30:211–221
Schmid M, Poppen A, Schmid W, Engel W (1981c) Somatic pairings of the Y heterochromatin in human XYY and XY qi cells. Cytogenet Cell Genet 29:203–214
Schwanitz G (1976) Die Normvarianten menschlicher Chromosomen. Perimed, Erlangen
Schweizer D, Ambros P, Andrle M (1978) Modification of DAPI banding on human chromosomes by prestaining with a DNA binding oligopeptide antibiotic, distamycin A. Exp Cell Res 111:327–332
Seabright M (1971) A rapid banding technique for human chromosomes. Lancet II:971–972
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 S, Halbrecht I (1983) Familial fragility on chromosome 16 (fra 16q22) enhanced by both interferon and distamycin A. Hum Genet 63:341–344
Sørensen K, Nielson J, Holm V, Haahr J (1979) Fragile site long arm chromosome 16. Hum Genet 48:131–139
Sumner AT (1972) A simple technique for demonstrating centromeric heterochromatin. Exp Cell Res 75:304–306
Sutherland GR (1979) Heritable fragile sites on human chromosomes. II. Distribution, phenotypic effects, and cytogenetics. Am J Hum Genet 31:136–148
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
Thestrup-Pedersen K, Bisballe S, Jensen JR, Esmann V, Heron I (1981) Epstein-Barr-virus and chromosomal defect: a family study. Lancet II:636–637
Zimmer C (1975) Effects of the antibiotics netropsin and distamycin A on the structure and function of nucleic acids. Prog Nucleic Acid Res Mol Biol 15:285–318
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schmid, M., Hungerford, D.A., Poppen, A. et al. The use of distamycin A in human lymphocyte cultures. Hum Genet 65, 377–384 (1984). https://doi.org/10.1007/BF00291563
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00291563