Radiation- and Drug-Induced DNA Repair in Mammalian Oocytes and Embryos

  • Roger A. Pedersen
  • Brigitte Brandriff
Part of the Basic Life Sciences book series (BLSC, volume 15)


A review of studies showing ultraviolet- or drug-induced unscheduled DNA synthesis in mammalian oocytes and embryos suggests that the female gamete has an excision repair capacity from the earliest stages of oocyte growth. The oocyte’s demonstrable excision repair capacity decreases at the time of meiotic maturation for unknown reasons, but the fully mature oocyte maintains a repair capacity, in contrast to the mature sperm, and contributes this to the zygote. Early embryo cells maintain relatively constant levels of excision repair until late fetal stages, when they lose their capacity for excision repair.

These apparent changes in excision repair capacity do not have a simple relationship to known differences in radiation sensitivity of germ cells and embryos.


Excision Repair Polar Body Germinal Vesicle Mouse Oocyte Meiotic Maturation 
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.


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  1. 1.
    Alexandre, H. L., Effects of x-irradiation on preimplantation mouse embryos cultured in vitro, J. Reprod. Fert., 36 (1974) 417–420.CrossRefGoogle Scholar
  2. 2.
    Baker, T. G., Radiosensitivity of mammalian oocytes with particular reference to the human female, Am. J. Obstet. Gynecol., 110 (1971) 746–761.PubMedGoogle Scholar
  3. 3.
    Baker, T. G., and A. McLaren, The effect of tritiated thymidine on the developing oocytes of mice, J. Reprod. Fert., 34 (1973) 121–130.CrossRefGoogle Scholar
  4. 4.
    Baker, T. G., and P. Neal, Action of ionizing radiations on the mammalian ovary, In: The Ovary, Ed. 2, Vol. 3, Regulation of Oogenesis and Steroidogenesis, L. Zuckerman and B. J. Weir, Eds., Academic Press, New York, 1977, pp. 1–58.Google Scholar
  5. 5.
    Bakken, A., Unpublished data.Google Scholar
  6. 6.
    Bodell, W. J., and M. R. Banerjee, The influence of chromatin structure on the distribution of DNA repair synthesis studied by nuclease digestion, Nucl. Acids Res., 6 (1979) 359–370.PubMedCrossRefGoogle Scholar
  7. 7.
    Bowden, G. T., J. E. Trosko, B. G. Shapas, and R. K. Boutwell, Excision of pyrimidine dimers from epidermal DNA and nonsemiconservative epidermal DNA synthesis following ultraviolet irradiation of mouse skin, Cancer Res., 35 (1975) 3599–3607.PubMedGoogle Scholar
  8. 8.
    Bowman, P., and A. McLaren, Cleavage rate of mouse embryos in vivo and in vitro, J. Embryol. Exptl. Morphol., 24 (1970) 203–207.Google Scholar
  9. 9.
    Brandriff, B., and R. A. Pedersen, Unpublished data.Google Scholar
  10. 10.
    Brazill, J. L., and Y. Masui, Changing levels of UV light and carcinogen-induced unscheduled DNA synthesis in mouse oocytes during meiotic maturation, Exptl. Cell Res., 112 (1978) 121–125.PubMedCrossRefGoogle Scholar
  11. 11.
    Brewen, J. G., H. S. Payne, and I. D. Adler, X-ray-induced chromosome aberrations in mouse dictyate oocytes, II. Fractionation and dose rate effects, Genetics, 87 (1977) 699–708.PubMedGoogle Scholar
  12. 12.
    Chandley, A. C., and S. Kofman-Alfaro, “Unscheduled” DNA synthesis in human germ cells following UV irradiation, Exptl. Cell Res. 69 (1971) 45–48.PubMedCrossRefGoogle Scholar
  13. 13.
    Chiquoine, A. D., The identification, origin, and migration of the primordial germ cells in the mouse embryo, Anat. Rec. 118 (1954) 135–146.PubMedCrossRefGoogle Scholar
  14. 14.
    Cleaver, J. E., DNA repair with purines and pyrimidines in radiation-and carcinogen-damaged normal and xeroderma pigmentosum human cells, Cancer Res., 33 (1973) 362–369.PubMedGoogle Scholar
  15. 15.
    Cleaver, J. E., Nucleosome structure controls rates of excision repair in DNA of human cells, Nature, 270 (1977) 451–453.PubMedCrossRefGoogle Scholar
  16. 16.
    Crone, M., Radiation stimulated incorporation of 3H-thymidine into diplotene oocytes of the guinea-pig, Nature, 228 (1970) 460.PubMedCrossRefGoogle Scholar
  17. 17.
    Crone, M., and H. Peters, Unusual incorporation of tritiated thymidine into early diplotene oocytes of mice, Exptl. Cell Res., 50 (1968) 664–668.PubMedCrossRefGoogle Scholar
  18. 18.
    Dempster, E. R., Absence of a time factor in the production of translocations in Drosophila sperm by x-irradiation, Am. Naturalist, 75 (1941) 184–187.CrossRefGoogle Scholar
  19. 19.
    Dobson, R. L., and M. F. Cooper, Tritium toxicity: effect of low-level 3HOH exposure on developing female germ cells in the mouse, Rad. Res., 58 (1974) 91–100.CrossRefGoogle Scholar
  20. 20.
    Dobson, R. L., C. G. Koehler, J. S. Felton, T. C. Kwan, B. J. Wuebbles, and D. C. L. Jones, Vulnerability of female germ cells in developing mice and monkeys to tritium, gamma rays, and polycyclic aromatic hydrocarbons, In: Developmental Toxicology of Energy-Related Pollutants, U.S. Department of Energy Symposium Series, 47 (1978) 1–14.Google Scholar
  21. 21.
    Ducibella, T., D. F. Albertini, E. Anderson, and J. D. Biggers, The preimplantation mammalian embryos: characterization of intercellular junctions and their appearance during development, Dev. Biol., 45 (1975) 231–250.PubMedCrossRefGoogle Scholar
  22. 22.
    DuFrain, R. J., The effects of ionizing radiation on preimplantation mouse embyros developing in vitro. In: Workshop on Basic Aspects of Freeze Preservation of Mouse Strains, O. Mühlbock, Ed., Gustav Fischer Verlag, Stuttgart, 1976, pp. 73–84.Google Scholar
  23. 23.
    DuFrain, R. J., and A. P. Casarett, Response of the pronuclear mouse embryo to x-irradiation in vitro, Rad. Res., 63 (1975) 494–500.CrossRefGoogle Scholar
  24. 24.
    Edwards, R. G., and A. G. Searle, Genetic radiosensitivity of specific post-dictyate stages in mouse oöcytes, Genet. Res., 4 (1963) 389–398.CrossRefGoogle Scholar
  25. 25.
    Eibs, H.-G., and H. Spielmann, Differential sensitivity of preimplantation mouse embryos to UV irradiation in vitro and evidence for post-replication repair, Rad. Res., 71 (1977) 367–376.CrossRefGoogle Scholar
  26. 26.
    Failla, P. M., Recovery from radiation-induced delay of cleavage in gametes of Arbacia punctulata, Science, 138 (1962) 1341–1342.PubMedCrossRefGoogle Scholar
  27. 27.
    Failla, P. M., Recovery from division delay in irradiated gametes of Arbacia punctulata, Rad. Res., 25 (1965) 331–340.CrossRefGoogle Scholar
  28. 28.
    Felton, J. S., T. C. Kwan, B. J. Wuebbles, and R. L. Dobson, Genetic differences in polycyclic-aromatic-hydrocarbon metabolism and their effects on oocyte killing in developing mice, In: Developmental Toxicology of Energy-Related Pollutants, U.S. Department of Energy Symposium Series, 47 (1978) 15–26.Google Scholar
  29. 29.
    Fisher, D. L., and M. Smithberg, In vitro and in vivo x-irradiation of preimplantation mouse embryos, Teratology, 7 (1973) 57–64.PubMedCrossRefGoogle Scholar
  30. 30.
    Reynolds, R. J., and E. C. Friedberg, Molecular mechanism of pyrimidine dimer excision in Saccharomyces cerevisiae. I. Studies with intact cells and cell-free systems, This volume, p. 121.Google Scholar
  31. 31.
    Generoso, W. M., Repair in fertilized eggs of mice and its role in the production of chromosomal aberrations, This volume, p. 411.Google Scholar
  32. 32.
    Generoso, W. M., K. T. Cain, M. Krishna, and S. W. Huff, Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg, Proc. Natl. Acad. Sci. (U.S.), 76 (1979) 435–437.CrossRefGoogle Scholar
  33. 33.
    Gledhill, B. L., and Z. Darzynkiewicz, Unscheduled synthesis of DNA during mammalian spermatogenesis in response to UV irradiation, J. Exptl. Zool., 183 (1973) 375–382.CrossRefGoogle Scholar
  34. 34.
    Goldstein, L. S., A. I. Spindle, and R. A. Pedersen, X-ray sensitivity of the preimplantation mouse embryo in vitro, Rad. Res., 62 (1975) 276–287.CrossRefGoogle Scholar
  35. 35.
    Hamilton, L., The influence of the cell cycle on the radiation response of early embryos, In: The Cell Cycle in Development and Differentiation, M. Balls and F. S. Billett, Eds., Cambridge University Press, 1973.Google Scholar
  36. 36.
    Hart, R. W., and R. B. Setlow, Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species, Proc. Natl. Acad. Sci. (U.S.), 71 (1974) 2169–2173.CrossRefGoogle Scholar
  37. 37.
    Henshaw, P. S., Studies of the effect of roentgen rays on the time of the first cleavage in some marine invertebrate eggs. I. Recovery from roentgen-ray effects in Arbacia eggs, Am. J. Roentgenol., 27 (1932) 890–898.Google Scholar
  38. 38.
    Hooverman, L. L., R. K. Meyer, and R. C. Wolf, Recovery from x-ray irradiation injury during delayed implantation in the rat, J. Endocrinol., 41 (1968) 75–84.CrossRefGoogle Scholar
  39. 39.
    Hsu, Y.-C., In vitro development of individually cultured whole mouse embryos from blastocyst to early somite stage, Dev. Biol. 68 (1979) 453–461.PubMedCrossRefGoogle Scholar
  40. 40.
    Kaufmann, B. P., The time interval between x-radiation of sperm of Drosophila and chromosome recombination, Proc. Natl. Acad. Sci. (U.S.), 27 (1941) 18–24.CrossRefGoogle Scholar
  41. 41.
    Kelly, S. J., J. G. Mulnard, and C. F. Graham, Cell division and cell allocation in early mouse development, J. Embryol. Exptl. Morphol., 48 (1978) 37–51.Google Scholar
  42. 42.
    Kirkpatrick, J. F., Radiation induced abnormalities in early in vitro mouse embryos, Anat. Rec., 176 (1973) 397–403.PubMedCrossRefGoogle Scholar
  43. 43.
    Kofman-Alfaro, S., and A. C. Chandley, Radiation-initiated DNA synthesis in spermatogenic cells of the mouse, Exptl. Cell Res., 69 (1971) 33–44.PubMedCrossRefGoogle Scholar
  44. 44.
    Krishna, M., and W. M. Generoso, Timing of sperm penetration, pronuclear formation, pronuclear DNA synthesis, and first cleavage in naturally ovulated mouse eggs, J. Exptl. Zool., 202 (1977) 245–252.CrossRefGoogle Scholar
  45. 45.
    Ku, K. Y., L. A. Moustafa, and P. Voytek, Induced DNA repair synthesis by ultraviolet radiation in mature mouse oocytes arrested in metaphase, II, IRCS Med. Sci., 3 (1975) 607.Google Scholar
  46. 46.
    Ku, K. Y., and P. Voytek, The effects of U.V.-light, ionizing radiation and the carcinogen N-acetoxy-2-fluorenylacetamide on the development in vitro of one-and two-cell mouse embryos, Intern. J. Rad. Biol., 30 (1976) 401–408.CrossRefGoogle Scholar
  47. 47.
    Lieberman, M. W., and P. D. Forbes, Demonstration of DNA repair in normal and neoplastic tissues after treatment with proximate chemical carcinogens and ultraviolet radiation, Nature, 241 (1973) 199–201.CrossRefGoogle Scholar
  48. 48.
    Lima-de-Faria, A., and K. Borum, The period of DNA synthesis prior to meiosis in the mouse, J. Cell Biol., 14 (1962) 381–388.PubMedCrossRefGoogle Scholar
  49. 49.
    Luthardt, F. W., and R. P. Donahue, Pronuclear DNA synthesis in mouse eggs: an autoradiographic study, Exptl. Cell Res., 82 (1973) 143–151.PubMedCrossRefGoogle Scholar
  50. 50.
    Lyon, M. F., and R. J. S. Phillips, Specific locus mutation rates after repeated small radiation doses to mouse oocytes, Mutat. Res., 30 (1975) 375–382.PubMedCrossRefGoogle Scholar
  51. 51.
    Lyon, M. F., and B. D. Smith, Species comparisons concerning radiation-induced dominant lethals and chromosome aberrations, Mutat. Res., 11 (1971) 45–58.PubMedCrossRefGoogle Scholar
  52. 52.
    Mandl, A. M., A quantitative study of the sensitivity of oocytes to x-irradiation, Proc. Roy. Soc. (London), B150 (1959) 53–71.Google Scholar
  53. 53.
    Mandl, A. M., The radiosensitivity of germ cells, Biol. Rev., 39 (1964) 288–371.PubMedCrossRefGoogle Scholar
  54. 54.
    Masui, Y., and R. A. Pedersen, Ultraviolet light-induced unscheduled DNA synthesis in mouse oocytes during meiotic maturation, Nature, 257 (1975) 705–706.PubMedCrossRefGoogle Scholar
  55. 55.
    Moor, R. M., and G. M. Warnes, Regulation of meiosis in mammalian oocytes, Brit. Med. Bull., 35 (1979) 99–103.PubMedGoogle Scholar
  56. 56.
    Mortelmans, K., E. C. Friedberg, H. Slor, G. Thomas, and J. E. Cleaver, Defective thymine dimer excision by cell-free extracts of xeroderma pigmentosum cells, Proc. Natl. Acad. Sci. (U.S.), 73 (1976) 2757–2761.CrossRefGoogle Scholar
  57. 57.
    Muller, H. J., An analysis of the process of structural change in chromosomes of Drosophila, J. Genet., 40 (1940) 1–66.CrossRefGoogle Scholar
  58. 58.
    Oakberg, E. F., Timing of oocyte maturation in the mouse and its relevance to radiation-induced cell killing and mutational sensitivity, Mutat. Res., 59 (1979) 39–48.PubMedCrossRefGoogle Scholar
  59. 59.
    Painter, R. B., and J. E. Cleaver, Repair replication, unscheduled DNA synthesis, and the repair of mammalian DNA, Rad. Res., 37 (1969) 451–466.CrossRefGoogle Scholar
  60. 60.
    Pedersen, R. A., Unpublished data.Google Scholar
  61. 61.
    Pedersen, R. A., and J. E. Cleaver, Repair of UV damage to DNA of implantation-stage mouse embryos in vitro, Exptl. Cell Res., 95 (1975) 247–253.PubMedCrossRefGoogle Scholar
  62. 62.
    Pedersen, R. A., and F. Mangia, Ultraviolet-light-induced unscheduled DNA synthesis by resting and growing mouse oocytes, Mutat. Res., 49 (1978) 425–429.PubMedCrossRefGoogle Scholar
  63. 63.
    Pedersen, T., Follicle growth in the mouse ovary, In: Oogenesis, J. D. Biggers and A. W. Schuetz, Eds., University Park Press, Baltimore, 1972, pp. 361–376.Google Scholar
  64. 64.
    Peleg, L., E. Raz, and R. Ben-Ishai, Changing capacity for DNA excision repair in mouse embryonic cells in vitro, Exptl. Cell Res., 104 (1976) 301–307.CrossRefGoogle Scholar
  65. 65.
    Regan, J. D., and R. B. Setlow, Two forms of repair in the DNA of human cells damaged by chemical carcinogens and mutagens, Cancer Res., 34 (1974) 3318–3325.PubMedGoogle Scholar
  66. 66.
    Russell, L. B., and C. S. Montgomery, Radiation-sensitivity differences within cell-division cycles during mouse cleavage, Intern. J. Rad. Biol., 10 (1966) 151–164.CrossRefGoogle Scholar
  67. 67.
    Russell, L. B., and W. L. Russell, An analysis of the changing radiation response of the developing mouse embryo, J. Cell Comp. Physiol., 43(Suppl. 1) (1954) 103–149.CrossRefGoogle Scholar
  68. 68.
    Russell, L. B., and W. L. Russell, The sensitivity of different stages in oogenesis to the radiation induction of dominant lethals and other changes in the mouse, In: Progress in Radiobiology, Proceedings of the Fourth International Conference on Radiobiology, J. S. Mitchell, B. E. Holmes, and C. L. Smith, Eds., Oliver and Boyd, Edinburgh, 1956, pp. 187–192.Google Scholar
  69. 69.
    Russell, W. L., Effect of the interval between irradiation and conception on mutation frequency in female mice, Proc. Natl. Acad. Sci. (U.S.), 54 (1965) 1552–1557.CrossRefGoogle Scholar
  70. 70.
    Russell, W. L., L. B. Russell, and E. M. Kelly, Radiation dose rate and mutation frequency, Science, 128 (1958) 1546–1550.PubMedCrossRefGoogle Scholar
  71. 71.
    Russell, W. L., L. B. Russell, and E. M. Kelly, Dependence of mutation rate on radiation intensity, In: Symposium on the Immediate and Low Level Effects of Ionizing Radiations, A. A. Buzzati-Traverso, Ed., Taylor and Francis, London, 1960, pp. 311–319.Google Scholar
  72. 72.
    Searle, A. G., Mutation induction in mice, In: Advances in Radiation Biology, Vol. 4, J. T. Lett, H. Adler, and M. Zelle, Eds., Academic Press, New York, 1974, pp. 131–207.Google Scholar
  73. 73.
    Sega, G. A., Unscheduled DNA synthesis in the germ cells of male mice exposed in vivo to the chemical mutagen ethyl methanesulfonate, Proc. Natl. Acad. Sci (U.S.), 71 (1974) 4955–4959.CrossRefGoogle Scholar
  74. 74.
    Sega, G. A., Relationship between unscheduled DNA synthesis and mutation induction in male mice, This volume, p. 373.Google Scholar
  75. 75.
    Sega, G. A., R. E. Sotomayor, and J. G. Owens, A study of unscheduled DNA synthesis induced by x-rays in the germ cells of male mice, Mutat. Res., 49 (1978) 239–257.PubMedCrossRefGoogle Scholar
  76. 76.
    Setlow, R. B., Repair deficient human disorders and cancer, Nature, 271 (1978) 713–717.PubMedCrossRefGoogle Scholar
  77. 77.
    Setlow, R. B., DNA repair pathways, This volume, p. 45.Google Scholar
  78. 78.
    Smerdon, M. J., T. D. Tlsty, and M. W. Lieberman, Distribution of ultraviolet-induced DNA repair synthesis in nuclease sensitive and resistant regions of human chromatin, Biochemistry, 17 (1978) 2377–2386.PubMedCrossRefGoogle Scholar
  79. 79.
    Snow, M. H. L., Abnormal development of pre-implantation mouse embryos grown in vitro with [3H]thymidine, J. Embryol. Exptl. Morphol., 29 (1973) 601–615.Google Scholar
  80. 80.
    Sorensen, R. A., and P. M. Wassarman, Relationship between growth and meiotic maturation of the mouse oocyte, Dev. Biol., 50 (1976) 531–536.PubMedCrossRefGoogle Scholar
  81. 81.
    Spielmann, H., and H.-G. Eibs, Recent progress in teratology: a survey of methods for the study of drug actions during the preimplantation period, Arzneim. Forsch., 28 (1978) 1733–1742.Google Scholar
  82. 82.
    Ward, W. F.H. Aceto, Jr., and M. Sandusky, Repair of sublethal and potentially lethal radiation damage by rat embryos exposed to gamma rays or helium ions, Radiology, 120 (1976) 695–700.PubMedGoogle Scholar
  83. 83.
    Ward, W. F., R. K. Meyer, and R. C. Wolf, Recovery from lethal x-ray damage during delayed implantation in the rat, J. Endocrinol., 51 (1971) 657–663.PubMedCrossRefGoogle Scholar
  84. 84.
    Ward, W. F., R. K. Meyer, and R. C. Wolf, Differential radio-sensitivity of rat blastocysts during delayed implantation, Proc. Soc. Exptl. Biol. Med., 140 (1973) 797–801.Google Scholar
  85. 85.
    Ward, W. F., R. K. Meyer, and R. C. Wolf, DNA synthesis in rat blastocysts x-irradiated during delayed implantation, Rad. Res., 55 (1973) 189–196.CrossRefGoogle Scholar
  86. 86.
    Wiley, L. M., and R. A. Pedersen, Morphology of mouse egg cylinder development in vitro: a light and electron microscopic study, J. Exptl. Zool., 200 (1977) 389–402.CrossRefGoogle Scholar
  87. 87.
    Würgler, F. E., and P. Maier, Genetic control of mutation induction in Drosophila melanogaster, I. Sex-chromosome loss in x-rayed mature sperm, Mutat. Res., 15 (1972) 41–53.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Roger A. Pedersen
    • 1
  • Brigitte Brandriff
    • 1
  1. 1.Laboratory of Radiobiology and Department of AnatomyUniversity of CaliforniaSan FranciscoUSA

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