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Cytological Methods for Detecting Chemical Mutagens

  • H. J. Evans
Chapter
Part of the Chemical Mutagens book series

Abstract

Chemical agents that induce mutations at specific loci in a eukaryote genome invariably also produce cytologically recognizable chromosome damage expressed as structural changes or “aberrations.” Moreover, many, and perhaps the majority, of the mutations induced in mammalian cell systems and detected through an alteration or loss of a given protein are associated with a visible cytological change involving the locus in question. In considering the possible action of chemical mutagens on man, it is important therefore to realize that spontaneous mutations in the form of chromosome aberrations(1)comprise a major part of man’s genetic burden; that certain of these aberrations are transmitted from generation to generation; and, as revealed from studies on laboratory animals, that the incidence of such aberrations must be increased on exposure of germ cells to mutagens.

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References

  1. 1.
    P. A. Jacobs, M. Melville, S. Ratcliffe, A. J. Keay, and J. Syme, A cytogenetic survey of 11,680 newborn infantsAnn. Hum. Genet. 37, 359–376 (1974).PubMedCrossRefGoogle Scholar
  2. 2.
    H. J. Evans, Chromosome aberrations induced by ionizing radiationsInt. Rev. Cytol. 13, 221–321 (1962).Google Scholar
  3. 3.
    H. J. Evans, Effects of ionizing radiation on mammalian chromosomes, in “Chromosomes and Cancer” (James German, ed.), pp. 191–237, John Wiley & Sons, New York (1974).Google Scholar
  4. 4.
    S. Wolff, Radiation genetics, in “Mechanisms in Radiobiology” (M. Errera and A. Forssberg, eds.). Vol. 1, pp. 419–475, Academic Press, Inc., New York (1961).Google Scholar
  5. 5.
    S. Wolff, Radiation genetics, in “Annual Review of Genetics” (H. L. Roman, L. S. Sandler, and G. S. Stent, eds.) Vol. 1, pp. 221–244, Annual Reviews Inc., Palo Alto, California (1967).Google Scholar
  6. 6.
    B. A. Kihlman, “Actions of chemicals on dividing cells,” Prentice-Hall Inc., New Jersey (1966).Google Scholar
  7. 7.
    H. J. Evans and D. Scott, Influence of DNA synthesis on the production of chromatid aberrations by X-rays and maleic hydrazideGenetics 49, 17–38 (1964).PubMedGoogle Scholar
  8. 8.
    H. J. Evans and D. Scott, The induction of chromosome aberrations by nitrogen mustard and its dependence on DNA synthesisProc. Roy. Soc. B 173, 491–512 (1969).CrossRefGoogle Scholar
  9. 9.
    K. E. Buckton and H. J. Evans, Methods for the analysis of human chromosome aberrations, WHO Publication, Geneva (1973).Google Scholar
  10. 10.
    D. E. Lea, “Actions of radiations on living cells,” Cambridge University Press (1955).Google Scholar
  11. 11.
    H. J. Evans, Repair and recovery from chromosome damage after fractionated X-ray dosage, in “Genetical Aspects of Radiosensitivity: Mechanisms of Repair,” pp. 31–48, International Atomic Energy Agency, Vienna (1966).Google Scholar
  12. 12.
    M. A. Bender, J. S. Bedford, and J. B. Mitchell, Mechanisms of chromosomal aberration production. II. Aberrations induced by 5-bromodeoxyuridine and visible lightMutation Res. 20, 403–416 (1973).PubMedCrossRefGoogle Scholar
  13. 13.
    J. A. Heddle and D. J. Bodycote, On the formation of chromosomal aberrationsMutat. Res. 9, 117–126 (1970).PubMedCrossRefGoogle Scholar
  14. 14.
    H. J. Evans, Population cytogenetics and environmental factors, in “Human Population Cytogenetics” (P. A. Jacobs, W. Price, and P. Law, eds.) Pfizer Medical Monographs 5, pp. 192–216, Edinburgh University Press (1970).Google Scholar
  15. 15.
    J. H. Taylor, Sister chromatid exchanges in tritium-labeled chromosomes. Genetics 43, 515–529 (1958).PubMedGoogle Scholar
  16. 16.
    J. G. Brewen and W. J. Peacock, The effect of tritiated thymidine on sister-chromatid exchange in a ring chromosomeMutat. Res.7, 433–440 (1969).PubMedCrossRefGoogle Scholar
  17. 17.
    D. A. Gibson and D. M. Prescott, Induction of sister chromatid exchanges in chromosomes of rat kangaroo cells by tritium incorporated into DNAExp. Cell Res. 74, 397–402 (1972).PubMedCrossRefGoogle Scholar
  18. 18.
    A. F. Zakharov and N. A. Egolina, Differential spiralization along mammalian mitotic chromosomes. I. BUdR-revealed differentiation in Chinese hamster chromosomesChromosoma 38, 341–365 (1972).PubMedCrossRefGoogle Scholar
  19. 19.
    S. A. Latt, Microfluorometric detection of deoxyribonucleic acid replication in human metaphase chromosomesProc. Nat. Acad. Sci. USA 70, 3395–3399 (1973).PubMedCrossRefGoogle Scholar
  20. 20.
    P. Perry and S. Wolff, New Giemsa method for the differential staining of sister chromatidsNature London 251, 156–158 (1974).PubMedCrossRefGoogle Scholar
  21. 21.
    S. Wolff and P. Perry, Differential Giemsa staining of sister chromatids and the study of sister chromatid exchanges without autoradiographyChromosoma 48, 341–353 (1974).PubMedCrossRefGoogle Scholar
  22. 22.
    S. A. Latt, Sister chromatid exchanges, indices of human chromosome damage and repair: detection by fluorescence and induction by mitomycin CProc. Nat. Acad. Sci. USA 71, 3162–3166 (1974).PubMedCrossRefGoogle Scholar
  23. 23.
    P. Perry and H.J. Evans, Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. Nature 258, 121–125 (1975).PubMedCrossRefGoogle Scholar
  24. 24.
    A. D. Conger, The fate of metaphase aberrationsRadiat. Bot. 5, 81–96 (1965).CrossRefGoogle Scholar
  25. 25.
    A. D. Conger and H. J. Curtis, Abnormal anaphases in regenerating mouse liversRadiat. Res. 33, 150–161 (1968).PubMedCrossRefGoogle Scholar
  26. 26.
    J. A. Heddle, A rapidin vivotest for chromosomal damageMutat. Res. 18, 187–190 (1973).PubMedCrossRefGoogle Scholar
  27. 27.
    W. Schmid, D. T. Arakaki, N. A. Breslau, and J. C. Culbertson, Chemical mutagenesis. The Chinese hamster bone marrow as anin vivotest system. 1. Cytogenetic results on basic aspects of the methodology obtained with alkylating agentsHumangenetik 11, 103–118 (1971).Google Scholar
  28. 28.
    M. Von Ledebur and W. Schmid, The micronucleus test. Methodological aspectsMutat. Res. 19, 109–117 (1973).CrossRefGoogle Scholar
  29. 29.
    W. Schmid, The micronucleus test. Mutation Res. 31, 9–15, (1975a).PubMedCrossRefGoogle Scholar
  30. 30.
    W. Schmid, The micronucleus test for cytogenetic analysis, in “Chemical Mutagens” (A. Hollaender, ed.), Vol. 4, pp. 31–53, Plenum Press, New York (1976).Google Scholar
  31. 31.
    H. J. Evans and M. L. O’Riordan, Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen testsMutat. Res. 31, 135–148 (1975).PubMedCrossRefGoogle Scholar
  32. 32.
    H. J. Evans, W. M. Court Brown, and A. McLean (eds.), “Human Radiation Cytogenetics,” sss North-Holland, Amsterdam (1967).Google Scholar
  33. 33.
    R. J. Preston, J. G. Brewen, and N. Gengozian, Persistence of radiation-induced chromosome aberrations in marmoset and manRadiat. Res. 60, 516–524 (1974).PubMedCrossRefGoogle Scholar
  34. 34.
    Report of UN Scientific Committee on Effects of Atomic Radiation, General Assembly, 24th Session, Suppl. 13 (A/7613), pp. 98–155, United Nations, New York (1969).Google Scholar
  35. 35A.
    C. Stevenson and C. Patel, Effects of chlorambucil on human chromosomesMutat. Res. 18, 333–351 (1973).PubMedCrossRefGoogle Scholar
  36. 36.
    G. Pollini and R. Colombi, II danno cromosomico dei linfociti nell’emopatia benzenicaMed. Lavoro 55, 641–654 (1964).Google Scholar
  37. 37.
    I. M. Tough and W. M. Court Brown, Chromosome aberrations and exposure to ambient benzene. Lancet i, 684.Google Scholar
  38. 38.
    I. M. Tough, P. G. Smith, W. M. Court Brown, and D. G. Harnden, Chromosome studies on workers exposed to atmospheric benzeneEur. J. Cancer 6, 49–55 (1970).PubMedCrossRefGoogle Scholar
  39. 39.
    M. N. Rabello, W. Becak, W. F. de Almeida, P. Pigati, M. T. Ungaro, T. Murata, and C. A. B. Pereira, Cytogenetic study on individuals occupationally exposed to DDTMutat. Res. 28, 449–454 (1975).CrossRefGoogle Scholar
  40. 40.
    G. Deknudt, A. Leonard, and B. Ivanov, Chromosome aberrations observed in male workers occupationally exposed to leadEnviron. Physiol. Biochem. 3, 132–138 (1973).Google Scholar
  41. 41.
    M. Bauchinger, E. Schmid, and D. Schmidt, Chromosomen-analyse bei Verkehrspolizisten mit Erhöhter BleilastMutat. Res. 16, 407–412 (1972).PubMedCrossRefGoogle Scholar
  42. 42.
    M. L. O’Riordan and H. J. Evans, Absence of significant chromosome damage in males occupationally exposed to lead. Nature 247, 50–53 (1974).PubMedCrossRefGoogle Scholar
  43. 43.
    Y. Shiraishi and T. H. Yosida, Chromosomal abnormalities in cultured leucocyte cells from Itai Itai disease patientsProc. Jpn Acad. 48, 248–251 (1972).Google Scholar
  44. 44.
    G. Deknudt and A. Leonard, personal communication (1975).Google Scholar
  45. 45.
    M. A. Pilinskya, Chromosome aberrations in persons in contact with ziram under industrial conditionsGenetika 6, 157 (1970).Google Scholar
  46. 46.
    W. W. Nichols, R. C. Miller, W. Heneen, C. Bradt, L. Hollister, and S. Kanter, Cytogenetic studies on human subjects receiving marihuana and A-9-tetrahydrocannabinolMutat. Res. 26, 413–417 (1974).PubMedCrossRefGoogle Scholar
  47. 47.
    C. E. Dick, M. L. Schniepp, R. C. Sonders, and R. G. Wiegand, Cyclamate and cyclohexylamine: lack of effect on the chromosomes of man and ratsin vivo, Mutat. Res. 26, 199–203 (1974).PubMedCrossRefGoogle Scholar
  48. 48.
    J. Yoder, M. Watson, and W. W. Benson, Lymphocyte chromosome analysis of agricultural workers during extensive occupational exposure to pesticidesMutat. Res. 21, 335–340 (1973).PubMedCrossRefGoogle Scholar
  49. 49.
    Ducatman, K. Hirschhorn, and I. J. Selikoff, Vinyl chloride exposure and human chromosome aberrations Mutat. Res. 31, 163–168 (1975).Google Scholar
  50. 50.
    J. H. Turner and D. L. Hutchinson, Cyclohexylamine mutagenicity: anin vivoevaluation utilizing fetal lambsMutat. Res. 26, 407–412 (1974).PubMedCrossRefGoogle Scholar
  51. 51.
    B. Beck and G. Obe, The human leukocyte test system. IL Different sensitivities of subpopulations to a chemical mutagenMutat. Res. 24, 395–398 (1973).CrossRefGoogle Scholar
  52. 52.
    G. Buchinger, Mutagenicity experiments with mice and human cell cultures: treatment with an acridine derivative (trypaflavin), in “Chemical Mutagenesis in Mammals and Man” (F. Vogel and G. Röhrborn, eds.), pp. 350–366, Springer-Verlag, Heidelberg (1970).CrossRefGoogle Scholar
  53. 53.
    D. G. Harnden, Skin culture and solid tumor technique in “Human Chromosome Methodology,” 2nd ed. (J. J. Yunis, ed.), pp. 167–184, Academic Press, New York (1974).CrossRefGoogle Scholar
  54. 54.
    U. Wolff, Cell cultures from tissue expiants in “Methods in Human Cytogenetics” (H. G. Schwarzacher, U. Wolf, and E. Passarge, eds.), pp. 39–58, Springer-Verlag, Berlin (1974).Google Scholar
  55. 55.
    P. R. Glade, J. A. Kasel, H. L. Moses, J. Whang-Peng, P. F. Hoffman, J. K. Kaumermeyer, and L. N. Chessin, Infectious mononucleosis: continuous suspension culture of peripheral blood leukocytes. Nature, 217, 564–565 (1968).PubMedCrossRefGoogle Scholar
  56. 56.
    C. M. Steel and E. Edmond, Human lymphoblastoid cell lines. I. Culture methods and examination for Epstein-Barr virus. Nat. Cancer Inst. 47, 1193–1202 (1971).Google Scholar
  57. 57.
    C. M. Steel, Human lymphoblastoid cell lines. III. Cocultivation technique for establishment of new lines. Nat. Cancer Inst. 48, 623–628 (1972).Google Scholar
  58. 58.
    E. Robbins and P. I. Marcus, Mitotically synchronized mammalian cells: a simple method for obtaining large populations. Science 144, 1152–1153 (1964).PubMedCrossRefGoogle Scholar
  59. 59.
    K. Ohama and T. Kadotani, Cytologic effects of Bleomycin on cultured human leukocytes, Jpn. J. Hum. Genet. 14, 293–297 (1970).Google Scholar
  60. 60.
    C. Promchainant, Cytogenetic effect of Bleomycin on human leukocytesin vitro, Mutat. Res. 28, 107–112 (1975).CrossRefGoogle Scholar
  61. 61.
    R. S. Bornstein, D. A. Hungerford, G. Haller, P. F. Engstrom, and J. W. Yarbro, Cytogenetic effects of Bleomycin therapy in man. Cancer Res. 31, 2004–2007 (1971).PubMedGoogle Scholar
  62. 62.
    J. G. Brewen, F. G. Pearson, K. P. Jones, and H. E. Luippold, Cytogenetic effects of cyclohexylamine and N-OH-cyclohexylamine on human leukocytes and Chinese hamster bone marrow. Nature New Biol. 230, 15–16 (1971).PubMedCrossRefGoogle Scholar
  63. 63.
    Paris Conference (1971): Standardization in Human Cytogenetics, “Birth Defects, Original Articel Series,” Vol. VIII, No. 7, The National Foundation—March of Dimes, New York (1972).Google Scholar
  64. 64.
    M. Bobrow, K. Madan, and P. L. Pearson, Staining of some specific regions of human chromosomes, particularly the secondary constriction of No. 9Nature New Biol. 238, 122–124 (1972).PubMedCrossRefGoogle Scholar
  65. 65.
    J. R. Gosden, A. R. Mitchell, R. A. Buckland, R. P. Clayton, and H. J. Evans, The location of four human satellite DNAs on human chromosomesExp. Cell Res. 92, 148–158 (1975).Google Scholar
  66. 66.
    S. I. Matsui and M. Sasaki, Differential staining of nucleolus organisers in mammalian chromosomes. Nature, 246, 148–150 (1973).PubMedCrossRefGoogle Scholar
  67. 67.
    B. Dutrillaux, Nouveau systeme de marquage chromosomique: Les bandes TChromosoma 41, 395–402 (1973).PubMedCrossRefGoogle Scholar
  68. 68.
    T. Caspersson, G. Limakka, and L. Zech, 24 fluorescence patterns of human metaphase chromosomes—distinguishing characters and variabilityHereditas 67, 89–102 (1971).CrossRefGoogle Scholar
  69. 69.
    H. J. Evans, K. E. Buckton, and A. T. Sumner, Cytological mapping of human chromosomes: results obtained with quinacrine fluorescence and the acetic-saline-giemsa techniques Chromosoma 35, 310–325 (1971).PubMedCrossRefGoogle Scholar
  70. 70.
    M. L. Pardue and J. G. Gall, Chromosomal localization of mouse satellite DNAScience 168, 1356–1358 (1970).PubMedCrossRefGoogle Scholar
  71. 71.
    F. E. Arrighi and T. C. Hsu, Localization of heterochromatin in human chromosomes. Cytogenetics 10, 81–86 (1971).PubMedCrossRefGoogle Scholar
  72. 72.
    A. T. Sumner, A simple technique for demonstrating centromeric heterochromatinExp. Cell Res. 75, 304–306 (1972).PubMedCrossRefGoogle Scholar
  73. 73.
    A. T. Sumner, H. J. Evans, and R. A. Buckland, A new technique for distinguishing between human chromosomes. Nature New Biol. 232, 31–32 (1971).PubMedCrossRefGoogle Scholar
  74. 74.
    M. E. Drets and M. W. Shaw, Specific banding patterns of human chromosomesProc. Nat. Acad. Sci. USA 68, 2073–2077 (1971).PubMedCrossRefGoogle Scholar
  75. 75.
    W. Schnedl, Analysis of the human karyotype using a reassociation techniqueChromosoma 34, 448–454 (1971).PubMedCrossRefGoogle Scholar
  76. 76.
    H. A. Lubs, W. H. McKenzie, S. R. Patil, and S. Merrick, New staining methods for chromosomes in “Methods in Cell Biology” (D. M. Prescott, ed.). Vol. VI, pp. 345–380, Academic Press, London (1973).Google Scholar
  77. 77.
    M. Seabright, A rapid banding technique for human chromosomesLancet 2, 971–972 (1971).PubMedCrossRefGoogle Scholar
  78. 78.
    B. Dutrillaux and J. Lejeune, Sur une nouvelle technique d’analyse du caryotype humain, C. R. Acad. Sci. Pans 272, 2638–2640 (1971).Google Scholar
  79. 79.
    J. Sehested, A simple method for R banding of human chromosomes, showing a pH-dependent connection between R and G bandsHumangenetik 21, 55–58 (1974).PubMedGoogle Scholar
  80. 80.
    T. Ikushima and S. Wolff, Sister chromatid exchanges induced by light flashes to 5-bromodeoxyuridine- and 5-iododeoxyuridine-substituted Chinese hamster chromosomesExp. Cell Res. 87, 15–19 (1974).PubMedCrossRefGoogle Scholar
  81. 81.
    T. Caspersson, U. Haglund, B Lindeel, and L. Zech, Radiation-induced non-random chromosome breakageExp. Cell Res. 75, 541–543 (1972).PubMedCrossRefGoogle Scholar
  82. 82.
    M. Holmberg and J. Jonasson, Preferential location of X-ray induced chromosome breakage in the R-bands of human chromosomesHereditas 74, 57–68 (1973).PubMedCrossRefGoogle Scholar
  83. 83.
    C. San Roman and M. Bobrow, The sites of radiation-induced breakage in human lymphocyte chromosomes, determined by quinacrine fluorescenceMutat. Res. 18, 325–331 (1973).CrossRefGoogle Scholar
  84. 84.
    M. Seabright, High-resolution studies on the patterns of induced exchanges in the human karyotypeChromosoma 40, 333–346 (1973).PubMedCrossRefGoogle Scholar
  85. 85.
    J. R. K. Savage, G. E. Watson, and T. R. L. Bigger, The participation of human chromosome arms in radiation-induced chromatid exchange in “Chromosomes Today” (J. Wahrman and K. R. Lewis, eds.). Vol. 4, pp. 267–276, John Wiley & Sons, New York, and Israel Universities Press, Jerusalem (1973).Google Scholar
  86. 86.
    A. Patino and H.J. Evans, in preparation.Google Scholar
  87. 87.
    D. R. Smyth and H. J. Evans, Mapping of sister-chromatid exchanges in human chromosomes using G-banding and autoradiographyMutat. Res.(in press).Google Scholar
  88. 88.
    S. A. Latt, Localization of sister chromatid exchanges in human chromosomes. Science 185, 74–76 (1974).PubMedCrossRefGoogle Scholar
  89. 89.
    M. M. Cohen and M. W. Shaw, Effects of mitomycin C on human chromosomesJ. Cell Biol. 23, 386–395 (1964).PubMedCrossRefGoogle Scholar
  90. 90.
    P. C. Nowell, Mitotic inhibition and chromosome damage by mitomycin in human leukocyte culturesExp. Cell Res. 33, 445–449 (1964).PubMedCrossRefGoogle Scholar
  91. 91.
    M. Morad, J. Jonasson, and J. Lindsten, Distribution of mitomycin C induced breaks on human chromosomesHereditas 74, 273–282 (1973).PubMedCrossRefGoogle Scholar
  92. 92.
    B. R. Reeves and C. Margóles, Preferential location of chlorambucil-induced breakage in the chromosomes of normal human lymphocytesMutat. Res. 26, 205–208 (1974).PubMedCrossRefGoogle Scholar
  93. 93.
    R. Howells and H.J. Evans, in preparation.Google Scholar

Copyright information

© Springer Science+Business Media New York 1976

Authors and Affiliations

  • H. J. Evans
    • 1
  1. 1.Medical Research Council Clinical and Population Cytogenetics UnitWestern General HospitalEdinburghUK

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