Induced Chromosomal Aberrations with Special Reference to Man

  • Kurt Hirschhorn
  • Maimon H. Cohen


Induced mutagenesis has long been an active and fruitful area of genetic research. The recent technical advances in tissue culture techniques, as well as in chromosome preparations, have greatly facilitated the expansion of this field to the chromosomal level. Four general classes of exogenous agents have been described which are capable of causing chromosome aberrations and, therefore, possibly gene mutations as well: irradiation, viruses, physical stimuli, and chemicals. This last group can be further subdivided into those compounds affecting biosynthesis of macromolecules (DNA, RNA, and protein): antitumor agents, antibiotics, alkylating agents, nitroso-compounds, and a heterogeneous miscellaneous group (Lea, 1955; Revell, 1953; Kihlman, 1961, 1966; Oster-tag, 1966; Cohen and Shaw, 1965).


Chromosomal Abnormality Chromosomal Aberration Centric Fusion Acrocentric Chromosome Pericentric Inversion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander, G. J., B. E. Miles, G. M. Gold and R. B. Alexander: LSD: injection early in pregnancy produces abnormalities in offspring of rats. Science 157:459, 1967.PubMedCrossRefGoogle Scholar
  2. Allison, A. C.: Chromosomes and neoplasia. European J. Cancer 5:481, 1968.Google Scholar
  3. Allison, A. C. and L. Mallucci: Histochemical studies of lysosomes and lysosomal enzymes in virus injected cell cultures. J. Exper. Med. 227:463, 1965.CrossRefGoogle Scholar
  4. Allison, A. C. and G. R. Paton: Chromosome damage in diploid cells following activation of lysosomal enzymes. Nature 207:1170, 1965.PubMedCrossRefGoogle Scholar
  5. Auerbach, R. and J. A. Rugowski: Lysergic acid diethylamide: effect on embryos. Science 255:1325, 1967.CrossRefGoogle Scholar
  6. Bender, L. and D. V. S. Sankar: Chromosome damage not found in leukocytes of children treated with LSD-25. Science 159:749, 1968.PubMedCrossRefGoogle Scholar
  7. Borgaonkar, D. S. and E. Gould: Homozygous reciprocal translocation as a mode of speciation in Microgale Thomas 1883 (Tenrecidae-Insectivora). Ex-perientia 24:506, 1968.Google Scholar
  8. Carr, D. H.: Chromosomes after oral contraceptives. Lancet ii:830, 1967.CrossRefGoogle Scholar
  9. Chessin, L. N.: Inherited variation of human somatic cells to poliovirus infection. M. D. Honors Thesis, New York University, 1963.Google Scholar
  10. Cohen, M. M.: The specific effects of streptonigrin activity on human chromosomes in culture. Cytogenetics 2:271, 1963.CrossRefGoogle Scholar
  11. Cohen, M. M. and M. W. Shaw: Effects of mitomycin C on human chromosomes. J. Cell Biol. 23:386, 1964.PubMedCrossRefGoogle Scholar
  12. Cohen, M. M. and M. W. Shaw: In Vitro, Vol. 2:50. Baltimore, Md.: Waverly Press, 1965.Google Scholar
  13. Cohen, M. M., M. W. Shaw and A. P. Craig: The effects of streptonigrin on cultured human leukocytes. Proc. Nat. Acad. Sci. U.S.A. 50:16, 1963.CrossRefGoogle Scholar
  14. Cohen, M. M., M. J. Marinello and N. Back: Chromosomal damage in human leukocytes induced by lysergic acid diethylamide. Science 255:1417, 1967a.CrossRefGoogle Scholar
  15. Cohen, M. M., K. Hirschhorn and W. A. Frosch: In vivo and in vitro chromosomal damage induced by LSD-25. New Eng. J. Med. 277:1043, 1967b.PubMedCrossRefGoogle Scholar
  16. Cohen, M. M., N. Takagi and E. K. Harrod: Trisomy D1 with two D/D translocation chromosomes. Am. J. Dis. Child. 225:185, 1968a.Google Scholar
  17. Cohen, M. M., K. Hirschhorn, S. Verbo, W. A. Frosch and M. M. Groeschel: The effect of LSD-25 on the chromosomes of children exposed in utero. Ped. Res. 2:486, 1968b.CrossRefGoogle Scholar
  18. Cohen, M. M., K. Hirschhorn and W. A. Frosch: Cytogenetic effects of tranquilizing drugs in vivo and in vitro. J.A.M.A. 207:2425, 1969.PubMedCrossRefGoogle Scholar
  19. Cohen, M. M. and A. B. Mukherjee: Meiotic chromosome damage induced by LSD-25. Nature 229:1072, 1968.CrossRefGoogle Scholar
  20. Darlington, C. D.: Misdivision and the genetics of the centromere. J. Genet. 37:341, 1939.CrossRefGoogle Scholar
  21. Darlington, C. D.: The origin of isochromosomes. J. Genet. 39:351, 1940.CrossRefGoogle Scholar
  22. Egozcue, J., S. Irwin and C. A. Maruffo: Chromosomal damage in LSD users. JAMA 204:214, 1968.PubMedCrossRefGoogle Scholar
  23. Elliot, W. H.: The effects of antimicrobial agents on deoxyribonucleic acid polymerase. Biochem. J. 86:562, 1963.Google Scholar
  24. Fetner, R. H.: Ozone-induced chromosome breakage in human cell cultures. Nature 194:793, 1962.PubMedCrossRefGoogle Scholar
  25. Geber, W. F.: Congenital malformations induced by mescaline, lysergic acid diethylamide and bromolysergic acid diethylamide in the hamster. Science 158:265, 1967.PubMedCrossRefGoogle Scholar
  26. Grossbard, L., D. Rosen, E. McGilvray, A. DeCapoa, O. J. Miller and A. Bank: Acute leukemia with Ph1 like chromosomes in an LSD user. JAMA 205:791, 1968.PubMedCrossRefGoogle Scholar
  27. Hirschhorn, K.: Abnormalities of the acrocentric chromosomes (abs). In: Genetics Today, Vol. 1. Proc. XI Int. Cong. Genetics. S. J. Geerts, ed., pp. 304–305, New York: Pergamon Press, 1965.Google Scholar
  28. Hirschhorn, K., L. Hsu and L. Strauss: Translocation-trisomy 13 in a child conceived after ingestion of LSD. (In preparation.) 1968a.Google Scholar
  29. Hirschhorn, K., N. Gersht and C. Friend: Chromosomal evolution in a human leukemic cell line by translocation. (In preparation.) 1968b.Google Scholar
  30. Hollowell, J. G. and L. G. Littlefield: Chromosome aberrations induced by plasma from irradiated patients. J. S. Carolina Med. Assoc. 53:437, 1967.Google Scholar
  31. Humphrey, R. M. and W. C. Dewey: Radiosensitivity of normal and 5-bromodeoxyuridine treated mammalian cells during different phases of the cell cycle. Exp. Cell Res. 39:483, 1965.PubMedCrossRefGoogle Scholar
  32. Irwin, S. and J. Egozcue: Chromosomal abnormalities in leukocytes from LSD-25 users. Science 157:313, 1967.PubMedCrossRefGoogle Scholar
  33. Iyer, V. N. and W. Szybalski: A molecular mechanism of mitomycin action: linking of complementary DNA strands. Proc. Nat. Acad. Sci. (Wash.) 50:355, 1963.CrossRefGoogle Scholar
  34. Jagiello, G.: Streptonigrin: effect of first meiotic metaphase of the mouse egg. Science 157:453, 1967.PubMedCrossRefGoogle Scholar
  35. Jarvik, L. G. and T. Kato: Is lysergide a teratogen? Lancet i:250, 1968.CrossRefGoogle Scholar
  36. Kersten, H.: Action of mitomycin C in nucleic acid metabolism in tumor and bacterial cells. Biochim. Biophys. Acta 55:558, 1962.PubMedCrossRefGoogle Scholar
  37. Kersten, H., W. Kersten, G. Leopold and B. Schnieders: Effect of mitomycin C on DNAse and RNA in Escherichia coli. Biochim. Biophys. Acta 80:521, 1964.PubMedGoogle Scholar
  38. Kihlman, B. A.: Biochemical aspects of chromosome breakage. Advances Genet. 10:1, 51, 1961.: Actions of Chemicals on Dividing Cells. Englewood Cliffs, N.J.: Prentice-Hall, Inc., 1966.Google Scholar
  39. Kury, G. and J. M. Craig: The effect of mitomycin C on developing chicken embryos. J. Embryol. Exp. Morph. 27:229, 1967.Google Scholar
  40. Lea, E. C.: Actions of Radiations on Living Cells. 2nd ed. Cambridge: University Press, 1955.Google Scholar
  41. Lieber, E., W. Seegers, K. Hirschhorn, P. Allderdice, A. DeCapoa and O. J. Miller: Apparent familial deletion of the short arm of chromosome 13 due to translocation. (In preparation.) 1968.Google Scholar
  42. Lisco, H. and E. Lisco: (Personal communication), 1968.Google Scholar
  43. Loughman, W. D., T. W. Sargent and D. M. Israelstam: Leukocytes of humans exposed to lysergic acid diethylamide: lack of chromosomal damage. Science 158:508, 1967.PubMedCrossRefGoogle Scholar
  44. Mallucci, L. and A. C. Allison: Lysosomal enzymes in cells infected with cyto-pathic and non-cytopathic viruses. J. Exper. Med. 121:477, 1965.CrossRefGoogle Scholar
  45. MacGregor, H. C. and H. G. Callan: The actions of enzymes on lampbrush chromosomes. Quart. J. Microscop. Sci. 103:113, 1962.Google Scholar
  46. Nusbacher, J. and K. Hirschhorn: Autosomal abnormalities. Adv. in Teratology (in press), 1968.Google Scholar
  47. Ostertag, W.: Chemische Mutagenese an menschlichen Zellen in Kultur. Abh. Math. Naturw. K1. 1:5, 1966.Google Scholar
  48. Ostertag, W. and J. Haake: The mutagenicity in Drosophila melanogaster of caffeine and of other compounds which produce chromosome breakage in human cells in culture. Z. Vererbungsl. 98:299, 1966.CrossRefGoogle Scholar
  49. Radding, C. M.: Incorporation of H3-thymidine by K12 (λ) induced by streptonigrin. In: Genetics Today. S. J. Geerts, ed. Oxford: Pergamon Press, p. 22, 1963.Google Scholar
  50. Reich, E.: Actinomycin: correlation of structure and function of its complexes with purines and DNA. Science 143:684, 1964.PubMedCrossRefGoogle Scholar
  51. Reveil, S. H.: Chromosome breakage by X-rays and radiomimetic substances in Vicia. In: Symposium on breakage. Heredity (Suppl.) 6:107, 1953.Google Scholar
  52. Schwartz, H. S., J. E. Sodergren and E. S. Philips: Mitomycin C.: Chemical and biological studies on alkylation. Science 142:1181, 1963.PubMedCrossRefGoogle Scholar
  53. Shaw, M. W. and M. M. Cohen: Chromosome exchanges in human leukocytes induced by mitomycin C. Genetics 57:181, 1965.Google Scholar
  54. Shaw, M. W. and E. Hayes: Effects of irradiated sucrose on the chromosomes of human lymphocytes in vitro. Nature 211:1254, 1966.PubMedCrossRefGoogle Scholar
  55. Skakkebaek, N. E., J. Phillip and O. J. Rafaelson: LSD in mice: abnormalities in meiotic chromosomes. Science 160:1246, 1968.PubMedCrossRefGoogle Scholar
  56. Somers, C. E. and R. M. Humphrey: A chromosome study of radiation sensitization by 5-bromodeoxyuridine. Exp. Cell Res. 30:208, 1963.PubMedCrossRefGoogle Scholar
  57. Sparkes, R. S., J. Melnyk and L. P. Bozzetti: Chromosomal effect in vivo of exposure to lysergic acid diethylamide. Science 260:1343, 1968.CrossRefGoogle Scholar
  58. Stacey, K. A., M. Cobb, S. F. Cousens and P. Alexander: The reactions of the “radiomimetic” alkylating agents with macromolecules in vitro. Ann. N.Y. Acad. Sci. 68:682, 1958.PubMedCrossRefGoogle Scholar
  59. Stenchever, M. A., R. Frankel, J. A. Jarvis and K. Veress: Some effects of Diazepam (Valium) on human cells in vitro. Amer. J. Obs. & Gyn. (in press), 1968.Google Scholar
  60. The Chicago Conference: Standardization in Human Cytogenetics. In: Birth Defects—Original Article Series Vol. II. Bergsma, Hamerton and Klinger, eds. Published by the National Foundation March of Dimes, 1966.Google Scholar
  61. Tough, I. M. and W. M. Court Brown: Chromosome aberrations and exposure to ambient benzene. Lancet i:684, 1965.CrossRefGoogle Scholar
  62. T’so, P. O. P., G. K. Helkamp and C. Sander: Interaction of nucleosides and related compounds with nucleic acids as indicated by the change of helix-coli transition temperature. Proc. Nat. Acad. Sci. (Wash.) 48:686, 1962.CrossRefGoogle Scholar
  63. T’so, P. O. P. and P. Lu: Interaction of nucleic acids. I. Physical binding of thymidine, adenine, steroids, and aromatic hydrocarbons to nucleic acids. Proc. Nat. Acad. Sci. (Wash.) 57:17, 1964.CrossRefGoogle Scholar
  64. Warig, M. J.: Complex formation with DNA and inhibition of Escherichia coli RNA polymerase by ethidium bromide. Biochim. Biophys. Acta 87:358, 1964.Google Scholar
  65. Warkany, J. and E. Takacs: Congenital malformations in rats from streptoni-grin. Arch. Path. 79:65, 1965.PubMedGoogle Scholar
  66. White, M. J. D.: The Chromosomes. Methuen’s Monographs on Biological Subjects. 5th ed. New York: John Wiley and Sons, 1961.Google Scholar
  67. Wolff, S.: Radiation studies on the nature of chromosome breakage. Amer. Nat. 94:85, 1960.CrossRefGoogle Scholar
  68. Wolff, S. and H. E. Luippold: Metabolism and chromosome break rejoining. Science 122:231, 1955.PubMedCrossRefGoogle Scholar
  69. Wuu, K. D. and W. F. Grant: Induced abnormal behavior in a barley plant (Hordeum vulgare, L.) with the herbicide Lorox. Phyton 23:63, 1966a.Google Scholar
  70. Wuu, K. D. and W. F. Grant: Morphological and somatic chromosomal aberrations induced by pesticides in barley (Hordeum volgare). Can. J. of Gen. and Cyt. 8:418, 1966b.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1969

Authors and Affiliations

  • Kurt Hirschhorn
    • 1
  • Maimon H. Cohen
    • 2
  1. 1.Division of Medical Genetics, Department of PediatricsMt. Sinai School of MedicineNew YorkUSA
  2. 2.Division of Human Genetics, Department of PediatricsState University of New York at Buffalo Medical School and Buffalo Children’s HospitalBuffaloUSA

Personalised recommendations