Human Peripheral Lymphocytes in Mutation Research

  • G. Obe
  • B. Beek

Abstract

Human peripheral lymphocyte (PL) cultures are a widely used test system for the analysis of chromosomal aberrations and sister chromatid exchanges (SCE), induced either in vivo or in vitro. The analysis of chromosomal aberrations and SCE’s in PL of exposed individuals still represents the only feasible method for the determination of mutagenic damage induced in man in vivo. The methodology and various aspects of “the human leukocyte test system” have been reviewed extensively (Buckton and Evans 1982; Crossen 1982; Gebhart 1982; Obe and Beek 1982a; Obe and Madle 1981; Natarajan and Obe 1980, 1982). In the following section we shall focus only on some special aspects and recent advantages concerning the “human leukocyte test system”, namely:
  1. 2.

    Stimulation of peripheral lymphocytes in vitro.

     
  2. 3.

    Inter-individual variabilities in induced chromosomal alterations and in repair capacities.

     
  3. 4.

    Intra-individual variabilities — the problem of subpopulations.

     
  4. 5.

    Fragile sites in human chromosomes.

     

Keywords

Polycyclic Aromatic Hydrocarbon Methotrexate Quinone Guanine Methoxy 

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References

  1. Agarwal SS, Loeb SS (1972) Studies on the induction of DNA polymerase during the transformation of human lymphocytes. Cancer Res 32:107–113PubMedGoogle Scholar
  2. Ahern T, Kay JE (1975) Protein synthesis and ribosome activation during the early stages of phytohemagglutinin lymphocyte stimulation. Exp Cell Res 92:513–515PubMedCrossRefGoogle Scholar
  3. Arrighi FE, Lau Y-F, Spallone A (1980) Nucleolar activity in differentiated cells after stimulation. Cytogenet Cell Genet 26:244–250PubMedCrossRefGoogle Scholar
  4. Beek B (1981a) BUdR-Giemsa labelling and satellite association in human leukocytes. Hum Genet 59:240–244PubMedCrossRefGoogle Scholar
  5. Beek B (1981b) Cell proliferation and chromosomal damage in human leukocytes: dicentrics and premature chromosome condensations in first, second, and third mitoses after X-irradia- tion. Hum Genet 57:75–77PubMedCrossRefGoogle Scholar
  6. Beek B (1982) X-ray-induced cell cycle delay in human leukocytes: differential response within the first poststimulation Gl-phase. Int J Radiat Biol 41:227–230CrossRefGoogle Scholar
  7. Beek B, Obe G (1974a) The human leukocyte test system. II. Different sensitivities of sub-populations to a chemical mutagen. Mutat Res 24:395–398PubMedCrossRefGoogle Scholar
  8. Beek B, Obe G (1974b) The effect of lead acetate on human leukocytes in vitro. Experientia 30: 1006–1007PubMedCrossRefGoogle Scholar
  9. Beek B, Obe G (1976) The human leukocyte test system. X. Higher sensitivity to X-irradiation in the GO-stage of the cell cycle of early as compared to late replicating cells. Hum Genet 35: 57–70PubMedCrossRefGoogle Scholar
  10. Beek B, Obe G (1977) Differential chromosomal radiosensitivity within the first Gl-phase of the cell cycle of early-dividing human leukocytes in vitro after stimulation with PHA. Hum Genet 35:209–218PubMedCrossRefGoogle Scholar
  11. Beek B, Obe G (1979) Sister chromatid exchanges in human leukocyte chromosomes: spontaneous and induced frequencies in early- and late-proliferating cells in vitro. Hum Genet 49:51 to 61Google Scholar
  12. Beek B, Jacky PB, Sutherland GR (1983a) Heritable fragile sites and micronucleus formation. Ann Genet 26:5–9Google Scholar
  13. Beek B, Jacky PB, Sutherland GR (1983b) DNA precursor deprivation-induced chromosomal damage. Mutat Res 113:331 (Abstr.)Google Scholar
  14. Beek B, Klein G, Obe G (1980) The fate of chromosomal aberrations in a proliferating cell system. Biol Zbl 99:73–84Google Scholar
  15. Bender MA, Brewen JG (1969) Factors influencing chromosome aberration yields in the human peripheral leukocyte system. Mutat Res 8:383–399PubMedCrossRefGoogle Scholar
  16. Bertazzoni U, Stefanini M, Dedrali Noy G, Giulotto E, Nuzzo F, Falaschi A, Spadari S (1976) Variations of DNA polymerase-a and ß during prolonged stimulation of human lymphocytes. Proc Natl Acad Sci USA 73:785–789PubMedCrossRefGoogle Scholar
  17. Bessis M (1973) Living blood cells and their ultrastructure. Springer, Berlin Heidelberg New YorkGoogle Scholar
  18. Bianchi NO, Bianchi MS, Larramendy M (1979) Kinetics of human lymphocyte division and chromosomal radiosensitivity. Mutat Res 63:317–324PubMedCrossRefGoogle Scholar
  19. Bianchi MS, Bianchi NO, Larramendy M, Garcia-Heras J (1981) Chromosomal radioselectivity of pig leukocytes in relation to sampling time. Mutat Res 80:313–320PubMedCrossRefGoogle Scholar
  20. Bianchi M, Bianchi NO, Brewen JG, Buckton KE, Fabry L, Fischer P, Gooch PC, Kucerova M, Leonard A, Mukheijee RN, Mukheq’ee U, Nakai S, Natarajan AT, Obe G, Palitti F, Pohl-Rüling J, Schwarzacher HG, Scott D, Sharma T, Takahashi E, Tanzarella C, van Buul PPW (1982) Evaluation of radiation-induced chromosomal aberrations in human peripheral blood lymphocytes in vitro. Result of an IAEA-coordinated programme. Mutat Res 96:233–242PubMedCrossRefGoogle Scholar
  21. Buckton KE, Evans HJ (1982) Human peripheral blood lymphocyte cultures: an in vitro assay for the cytogenetic effects of environmental mutagens. In: Hsu TC (ed) Cytogenetic assays of environmental mutagens. Allanheld Osmun, Totowa New York, pp 183–202Google Scholar
  22. Buckton KE, Pike MC (1964) Chromosome investigations of lymphocytes from irradiated patients: effect of time in culture. Nature 202:714–715PubMedCrossRefGoogle Scholar
  23. Bushkell LL, Kersey JA, Cervenka J (1976) Chromosomal breaks in T and B lymphocytes in Fanconi’s anemia. Clin Genet 9:583–587PubMedCrossRefGoogle Scholar
  24. Buul PPW van, Natarajan AT (1980) Chromosomal radiosensitivity of human leukocytes in relation to sampling time. Mutat Res 70:61–69PubMedCrossRefGoogle Scholar
  25. Cantor H (1981) Regulation of immune responses: analysis with lymphocyte clones. Cell 25:7–8PubMedCrossRefGoogle Scholar
  26. Carrano AV, Minkler JL, Stetka DG, Moore DH (1980) Variation in the baseline sister chromatid exchange frequency in human lymphocytes. Environ Mutagen 2:325–337PubMedCrossRefGoogle Scholar
  27. Coleman MS, Hutton JJ, Bollum FJ (1974) Terminal riboadenylate transferase in human lymphocytes. Nature 248:407–409PubMedCrossRefGoogle Scholar
  28. Cooper HL, Braverman R (1980) Protein synthesis in resting and growth-stimulated human peripheral lymphocytes. Evidence for regulation by a non-messenger RNA. Exp Cell Res 127: 351–359PubMedCrossRefGoogle Scholar
  29. Crossen PE (1982) SCE in lymphocytes. In: Sandberg AA (ed) Sister chromatid exchange. Liss, New York, pp 175–193Google Scholar
  30. Evans HJ (1982) Sister chromatid exchanges and disease states in man. In: Wolff S (ed) Sister chromatid exchange. Wiley, New York, pp 183–228Google Scholar
  31. Evans HJ, Vijayalaxmi XX (1980) Storage enhances chromosome damage after exposure of human leukocytes to mitomycin C. Nature 284:370–372PubMedCrossRefGoogle Scholar
  32. Forell B, Meyers LS Jr, Norman A (1982) DNA repair synthesis in minimally stressed human lymphocytes. Int J Radiat Biol 41:535–545CrossRefGoogle Scholar
  33. Gebhart E (1982) The epidemiological approach: chromosome aberrations in persons exposed to chemical mutagens. In: Hsu TC (ed) Cytogenetic assays of environmental mutagens. Allanheld Osmun, Totowa New York, pp 385–408Google Scholar
  34. Gibas Z, Limon J (1979) The induction of sister-chromatid exchanges by 9-aminoaeridine derivatives. I. The relation between the yield of SCE induction and cell kinetics in cultured human lymphocytes. Mutat Res 67:93–96PubMedCrossRefGoogle Scholar
  35. Giulotto E, Mottura A, Giorgi R, de Carli L (1980) Frequencies of sister-chromatid exchanges in relation to cell kinetics in lymphocyte cultures. Mutat Res 70:343–350PubMedCrossRefGoogle Scholar
  36. Hamlet SM, Lavin MF, Jennings PA (1982) Increased rate of repair of ultraviolet-induced DNA strand breaks in mitogen stimulated lymphocytes. Int J Radiat Biol 41:483–491CrossRefGoogle Scholar
  37. Harris H (1968) Nucleus and cytoplasm. Clarendon, OxfordGoogle Scholar
  38. Harris H (1970) Cell Fusion. Clarendon, OxfordGoogle Scholar
  39. Heddle JA, Evans HJ, Scott D (1967) Sampling time and the complexity of the human leukocyte culture system. In: Evans HJ, Court-Brown WM, McLean AS (eds) Human radiation cytogenetics. Elsevier/North-Holland, Amsterdam, pp 6–19Google Scholar
  40. Hedner K, Hôgstedt B, Kolnig A-M, Mark-Vendel E, Strômbeek B, Mitelman F (1982) Sister chromatid exchanges and structural chromosome aberrations in relation to age and sex. Hum Genet 62:305–309PubMedCrossRefGoogle Scholar
  41. Hittelman WN, Rao PN (1976) Premature chromosome condensation: Conformational changes of chromatin associated with phytohemagglutinin stimulation of peripheral lymphocytes. Exp Cell Res 100:219–222PubMedCrossRefGoogle Scholar
  42. Jacky PB, Beek B, Sutherland GR (1983) Fragile sites in chromosomes: possible model for the study of spontaneous chromosome breakage. Science 220:69–70PubMedCrossRefGoogle Scholar
  43. Jaehning J A, Stewart CC, Roeder RG (1975) DNA-dependent RNA polymerase levels during the response of human peripheral lymphocytes to phytohem agglutinin. Cell 4:51–57PubMedCrossRefGoogle Scholar
  44. Johnstone AP, Williams GT (1982) Role of DNA breaks and ADP-ribosyl transferase activity in eukaryotic differentiation demonstrated in human lymphocytes. Nature 300:368–370PubMedCrossRefGoogle Scholar
  45. Kay JE, Ahern T, Atkins M (1971) Control of protein synthesis during the activation of lymphocytes by phytohem agglutinin. Biochem Biophys Acta 247:322–334PubMedGoogle Scholar
  46. Killander D, Rigler R (1965) Initial changes of deoxyribonucleoprotein and synthesis of nucleic acid in phytohemagglutinin-stimulated human leukocytes in vitro. Exp Cell Res 39:701–704PubMedCrossRefGoogle Scholar
  47. Killander D, Rigler R (1969) Activation of deoxyribonucleoprotein in human leukocytes stimulated by phytohemagglutinin. I. Kinetics of the binding of acridine orange to deoxyribonucleoprotein. Exp Cell Res 54:163–170PubMedCrossRefGoogle Scholar
  48. Kim MA (1974) Chromatidaustausch und Heterochromatinverânderungen menschlicher Chromosomen nach BUdR-Markierung. Hum Genet 25:179–188CrossRefGoogle Scholar
  49. Klimov NA, Vashchenko VI, Kolyubaeva SN, Komar VE (1982) Changes in the supercoiled structure of nuclear DNA in rat and human peripheral blood lymphocytes after 7-irradiation. Int JRadiat Biol 41:221–225CrossRefGoogle Scholar
  50. Kwan DK, Norman A (1977) Radiosensitivity of human lymphocytes and thymocytes. Radiat Res 69:143–151PubMedCrossRefGoogle Scholar
  51. Lambert B, Ringborg U, Swanbeck G (1976) Ultraviolet-induced DNA repair synthesis in lymphocytes from patients with actinic keratosis. J Invest Dermatol 67:594–598PubMedCrossRefGoogle Scholar
  52. Lambert B, Ringborg U, Swanbeck G (1977) Repair of UV-induced DNA lesions in peripheral lymphocytes from healthy subjects of various ages, individuals with Down’s syndrome and patients with actinic keratosis. Mutat Res 46:133–134Google Scholar
  53. Lambert B, Ringborg U, Skoog L (1979) Age-related decrease of ultraviolet light-induced DNA repair synthesis in human peripheral leukocytes. Cancer Res 39:2792–2795PubMedGoogle Scholar
  54. Lambert B, Lindblad A, Holmberg K, Francesconi D (1982) The use of sister chromatid exchange to monitor human populations for exposure to toxicologically harmful agents. In: Wolff S (ed) Sister chromatid exchange. Wiley, New York, pp 149–182Google Scholar
  55. Léonard A, Decat G (1979) Relation between cell cycle and yield of aberrations observed in irradiated human lymphocytes. Can J Genet Cytol 21:473–478PubMedGoogle Scholar
  56. Lezana EA, Bianehi NO, Zabala-Suarez JE (1977) Sister chromatid exchanges in Down syndromes and normal human beings. Mutat Res 45:85–90PubMedCrossRefGoogle Scholar
  57. Lindblad A, Lambert B (1981) Relation between sister chromatid exchange, cell proliferation and proportion of B and T cells in human lymphocyte cultures. Hum Genet 57:31–34PubMedCrossRefGoogle Scholar
  58. Ling NR, Kay JE (1975) Lymphocyte stimulation. North-Holland, AmsterdamGoogle Scholar
  59. Littlefield LG, Colyer SP, DuFrain RJ (1983) SCE evaluations in human lymphocytes after GO exposure to mitomycin C. Lack of expression of MMC-induced SCEs in cells that have undergone greater than two in vitro divisions. Mutat Res 107:119–130PubMedCrossRefGoogle Scholar
  60. Loeb LA, Agarwal SS,Woodside AM (1968) Induction of DNA polymerase in human lymphocytes by phytohemagglutinin. Proc Natl Acad Sci USA 61:827–834PubMedCrossRefGoogle Scholar
  61. Loeb LA, Ewald JL, Agarwal SS (1970) DNA polymerase and DNA replication during lymphocyte transformation. Cancer Res 30:2514–2520PubMedGoogle Scholar
  62. Martin TE, Okamura CS (1981) hn RNP protein distribution in various differentiated vertebrate cells. In: Schweiger HG (ed) International cell biology 1980–1981. Springer, Berlin Heidelberg New York, pp 77–84Google Scholar
  63. Mattevi MS, Salzano FM (1975) Effect of sex, age, and cultivation time on number of satellite and acrocentric associations in man. Humangenetik 29:265–270PubMedCrossRefGoogle Scholar
  64. Mayer RJ, Smith RG, Gallo RC (1975) DNA-metabolizing enzymes in normal human lymphoid cells. VI. Induction of DNA polymerases a, ß, andy following stimulation with phytohemag- glutinin. Blood 46:509–518PubMedGoogle Scholar
  65. Morimoto K, Wolff S (1980) Increase of sister chromatid exchanges and pertubations of cell division kinetics in human lymphocytes by benzene metabolites. Cancer Res 40:1189–1193PubMedGoogle Scholar
  66. Nankin HR (1970) In vitro alterations of satellite association and nucleolar persistence in mitotic human lymphocytes. Cytogenetics 9:42–51PubMedCrossRefGoogle Scholar
  67. Natarajan AT, Obe G (1980) Screening of human populations for mutations induced by environmental pollutants: use of human lymphocyte system. Ecotoxicol Environm Safety 4:468–481CrossRefGoogle Scholar
  68. Natarajan AT, Obe G (1982) Mutagenicity testing with cultured mammalian cells: cytogenetic assays. In: Heddle JA (ed) Mutagenicity. New Horizons in genetic toxicology. Academic, New York, pp 171–213Google Scholar
  69. Natarajan AT, Meijers M, van Rijn JLS (1982) Individual variability of human cells in induction of chromosomal aberrations by mutagens. In: Sorsa M, Vainio H (eds) Mutagens in our environment. Liss, New York, pp 75–88Google Scholar
  70. Noel B, Quack B, Mottet J, Nantois Y, Dutrillaux B (1977) Selective endoreduplication or branched chromosome? Exp Cell Res 104:423–426PubMedCrossRefGoogle Scholar
  71. Nowell PC (1960) Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res 20:462–466PubMedGoogle Scholar
  72. Obe G, Beek B (1982a) The human leukocyte test system. In: deSerres FJ, Hollaender A (eds) Chemical mutagens. Principles and methods for their detection. Plenum, New York, vol 7, pp 337–400Google Scholar
  73. Obe G, Beek B (1982b) Premature chromosome condensation in micronuclei. In: Rao PN, Johnson RT, Sperling K (eds) Premature chromosome condensation: application in basic, clinical, and mutation research. Academic, New York, pp 113–130Google Scholar
  74. Obe G, Madie S (1981) Prüfung der Mutagenität von Medikamenten beim Menschen. Prax Pneumol 35:1027–1033Google Scholar
  75. Obe G, Beek B, Slacik-Erben R (1976) The use of the human leukocyte test system for the evaluation of potential mutagens. Excerpta Med 376:118–126. Elsevier/North-Holland, AmsterdamGoogle Scholar
  76. Obe G, Kaiweit S, Nowak C, Ali-Osman F (1982) Liquid holding experiments with human peripheral lymphocytes. I. Effects of liquid holding on sister chromatid exchanges induced by trenimon, diepoxybutane, bleomycin, and X-rays. Biol Zbl 101:97–113Google Scholar
  77. Ockey CH (1980) Differences between“spontaneous” and induced sister-chromatid exchanges with fixation time and their chromosome localization. Cytogenet Cell Genet 26:223–235PubMedCrossRefGoogle Scholar
  78. Oppenheim JJ, Rosenstreich DL (eds) (1976) Mitogens in immunobiology. Academic, NewYorkGoogle Scholar
  79. Otto B (1977) DNA-dependent ATPases in concanavalin A stimulated lymphocytes. FEBS Lett 97:175–178CrossRefGoogle Scholar
  80. Paigen B, Ward E, Reilly A, Houten L, Gurtoo HL, Minowada J, Steenland K, Havens MB, Sartori P (1981) Seasonal variation of aryl hydrocarbon hydroxylase activity in human lymphocytes. Cancer Res 41:2757–2761PubMedGoogle Scholar
  81. Pedrali Noy GCF, Dalpra L, Pedrini AM, Ciarrocchi G, Giulotto E, Nuzzo F, Falaschi A (1974) Evidence for two waves of induction of DNA enzymes in stimulated human lymphocytes. Nucleic Acids Res 1:1183–1189CrossRefGoogle Scholar
  82. Pero RW, Mitelman F (1979) Another approach to in vivo estimation of genetic damage in humans.Proc Natl Acad Sei USA:462–463Google Scholar
  83. Pero RW, Bryngelsson C, Mitelman F, Thulin T, Norddn Ä (1976) High blood pressure related to carcinogen-induced unscheduled DNA synthesis, DNA carcinogen binding, and chromosomal aberrations in human lymphocytes. Proc Natl Acad Sei USA 73:2496–2500CrossRefGoogle Scholar
  84. Pero RW, Bryngelsson C, Mitelman F, Kornfält R, Thulin T, Norddn Ä (1978) Interindividual variation in the responses of cultured human lymphocytes to exposure from DNA damaging chemical agents. Interindividual variation to carcinogen exposure. Mutat Res 53:327–341PubMedGoogle Scholar
  85. Petrzilka GE, Schroeder HE (1979) Activation of human T-lymphocytes. A kinetic and stereological study. Cell Tissue Res 201:101–127PubMedCrossRefGoogle Scholar
  86. Polet H, Spieker-Polet H (1980) Role of nuclear proteins on (3 H)actinomycin D binding during lymphocyte mitogenesis. Exp Cell Res 128:419–429PubMedCrossRefGoogle Scholar
  87. Prosser JS (1976) Survival of human T and B lymphocytes after X-irradiation. Int J Radiat Biol 30:459–465CrossRefGoogle Scholar
  88. Rahmsdorf HJ, Ponta H, Bäehle M, Mallick U, Weibezahn K-F, Herrlich P (1981) Differentiated cells from BALB/c mice differ in their radiosensitivity. Exp Cell Res 136:111–117PubMedCrossRefGoogle Scholar
  89. Riedel L, Obe G (1980) Trenimon-induced SCE sand structural chromosomal aberrations in early- and late-dividing lymphocytes. Mutat Res 73:125–131PubMedCrossRefGoogle Scholar
  90. Rigas D, Eginitis-Rigas C, Bigley RH, Stankova L, Head C (1980) Biphasic radiosensitization of human lymphocytes by diethyldithiocarbamate: possible involvement of superoxide dismutase. Int J Radiat Biol 38:257–266CrossRefGoogle Scholar
  91. Rigler R, Killander D (1969) Activation of deoxyribonucleoprotein in human leukocytes stimulated by phytohemagglutinin. II. Structural changes of deoxyribonucleoprotein and synthesis of RNA. Exp Cell Res 54:171–180PubMedCrossRefGoogle Scholar
  92. Santesson B, Lindahl-Kiessling K, Mattson A (1979) SCE in B and T lymphocytes: possible implications for Bloom’s syndrome. Clin Genet 16:133–135PubMedCrossRefGoogle Scholar
  93. Santos-Mello R, Kwan D, Norman A (1974) Chromosome aberrations and T-cell survival in human lymphocytes. Radiat Res 60:482–488PubMedCrossRefGoogle Scholar
  94. Schmiady H (1979) Die Länge vorzeitig kondensierter Chromosomen (PCC) und Chromosomenabschnitte menschlicher Zellen in Abhängigkeit vom Zellzyklus. Thesis, Freie Universität BerlinGoogle Scholar
  95. Schmiady H, Münke M, Sperling K (1979) Ag-staining of nucleolus organizer regions on human prematurely condensed chromosomes from cells with different ribosomal RNA gene activity. Exp Cell Res 121:425–428PubMedCrossRefGoogle Scholar
  96. Schneider EL (1982) Aging and sister chromatid exchange. In: Sandberg AA (ed) Sister chromatid exchange. Liss, New York, pp 195–203Google Scholar
  97. Schwartz JL, Gaulden ME (1980) The relation contributions of B and T lymphocytes in the human peripheral blood mutagen test system as determined by cell survival, mitogenic stimulation, and induction of chromosome aberrations by radiation. Environ Mutagen 2:473–485PubMedCrossRefGoogle Scholar
  98. Schwartz JL, Darr JC, Gaulden ME (1983) Survival and PHA-stimulation of 7-irradiated human peripheral blood T lymphocyte subpopulations. Mutat Res 107:413–425PubMedCrossRefGoogle Scholar
  99. Schwarzacher HG, Wachtier F (1983) Nucleolus organizer regions and nucleoli. Hum Genet 63: 89–99PubMedCrossRefGoogle Scholar
  100. Schwarzacher HG, Mikelsaar A-V, Schnedl W (1978) The nature of Ag-staining of nucleolus organizer regions. Electron- and light-microscopic studies on human cells in interphase, mitosis, and meiosis. Cytogenet Cell Genet 20:24–39PubMedCrossRefGoogle Scholar
  101. Scott D, Lyons CY (1979) Homogeneous sensitivity of human peripheral blood lymphocytes to radiation-induced chromosome damage. Nature 278:756–758PubMedCrossRefGoogle Scholar
  102. Sigmund J, Schwarzacher HG, Mikelsaar A-V (1979) Satellite association frequency and number of mucleoli depend on cell cycle duration and NOR-acitivty. Studies on first, second, and third mitoses of lymphocyte cultures. Hum Genet 50:81–91PubMedCrossRefGoogle Scholar
  103. Snope AJ, Rary JM (1979) Cell-cycle duration and sister chromatid exchange frequency in cultured human lymphocytes. Mutat Res 63:345–349PubMedCrossRefGoogle Scholar
  104. Steffen JA, Michalowski A (1973) Heterogeneous chromosomal radiosensitivity of phytohemagglutinin-stimulated human blood lymphocytes in culture. Mutat Res 17:367–376PubMedCrossRefGoogle Scholar
  105. Steffen JA, Swierkowska K, Michalowski A, Kling E, Nowakowska A (1978) In vitro kinetics of human lymphocytes activated by mitogens. In: Evans HJ, Lloyd DC (eds) Mutagen-induced chromosome damage in man. Edinburgh University Press, Edinburgh, pp 89–107Google Scholar
  106. Sutherland GR (1979a) Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culture. Am J Hum Genet 31:125–135PubMedGoogle Scholar
  107. Sutherland GR (1979b) Heritable fragile sites on human chromosomes. II. Distribution, phenotypic effects, and cytogenetics. Am J Hum Genet 31:136–148PubMedGoogle Scholar
  108. Sutherland GR (1983) The fragile X chromosome. Int Rev Cytol 81:107–143PubMedCrossRefGoogle Scholar
  109. Sutherland GR, Hinton L (1981) Heritable fragile sites on human chromosomes. VI. Characterisation of the fragile site at 12ql3. Human Genet 57:217–219CrossRefGoogle Scholar
  110. Sutherland GR, Jacky PB, Baker E, Manuel A (1983) Heritable fragile sites on human chromosomes. X. New folate sensitive fragile sites: 6p23, 9p21, 9q32, llq23. Am J Hum Genet 35: 432–437PubMedGoogle Scholar
  111. Szczylik C, Wiktor-Jedrzejczak W (1981) The effect of X-irradiation in vitro on subpopulations of human lymphocytes. Int J Radiat Biol 39:253–263CrossRefGoogle Scholar
  112. Trepel F (1975) Kinetik lymphatischer Zellen. In: Theml H, Begeman H (eds) Lymphozyt und klinische Immunologie. Springer, Berlin Heidelberg New York, pp 16–26Google Scholar
  113. Trepel F (1976) Das lymphatische Zellsystem: Struktur, allgemeine Physiologie und allgemeine Pathophysiologie. In: Begemann H (ed) andb Inn Medizin, Bd 2, Teil 3. Springer, Berlin Heidelberg New York, pp 1–191Google Scholar
  114. Tyrsted G, Munch-Petersen B, Cloos L (1973) DNA polymerase activity in phytohemagglutin instimulated and non-stimulated human lymphocytes. Exp Cell Res 77:415–427PubMedCrossRefGoogle Scholar
  115. Wachtier F, Ellinger A, Schwarzacher HG (1980) Nucleolar changes in human phytohemagglutinin-stimulated lymphocytes. Cell Tissue Res 213:351–360Google Scholar
  116. Waldstein EA, Cao E-H, Bender MA, Setlow RB (1982) Abilities of extracts of human lymphocytes to remove O6 -methylguanine from DNA. Mutât Res 95:405–416PubMedCrossRefGoogle Scholar
  117. Wyszynska K, Liniecki J (1980) The yield of radiation-induced chromosomal aberrations in lymphocytes as related to the time of arrival at first, poststimulation mitosis. Mutat Res 73: 101–114PubMedCrossRefGoogle Scholar
  118. Yew F-H, Johnson RT (1978) Human B and T lymphocytes differ in UV-induced repair capacity. Exp Cell Res 113:227–231PubMedCrossRefGoogle Scholar
  119. Yew F-H, Johnson RT (1979a) Ultravioletrinduced DNA excision repair in human B and T lymphocytes. II. Effects of inhibitors and DNA precursors. Biochem Biophys Acta 562:240–251PubMedGoogle Scholar
  120. Yew F-H, Johnson RT (1979b) Ultraviolet-induced DNA excision repair in human B and T lymphocytes. III. Repair in lymphocytes from chronic lymphocytic leukemia. J Cell Sei 39:329–337Google Scholar
  121. Zöllner EJ, Reitz M, Zahn RK, Slor H (1979) Deoxyribonucleases in phytohemagglutinin-stimulat- ed lymphocytes. Exp Cell Res 123:365–369PubMedCrossRefGoogle Scholar
  122. Zöllner EJ, Störger H, Breter H-J, Zahn RK (1975) Characterization of different deoxyribonucleases in human lymphocytes. Z Naturforsch 30c:781–784Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • G. Obe
    • 1
  • B. Beek
    • 2
  1. 1.Institut für GenetikFreie Universität BerlinGermany
  2. 2.Umweltbundesamt BerlinGermany

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