Relationship of DNA Lesions and their Repair to Chromosomal Aberration Production

  • Michael A. Bender
Part of the Basic Life Sciences book series (BLSC, volume 15)


Though the roles of some specific DNA lesions in the production of chromosomal aberrations is clearly established, those of others remain unclear. While the study of aberration production in human genetic DNA repair deficiency diseases has been extremely rewarding already, eukaryotic repair systems are obviously complex, and one is tempted to feel that such studies may have raised as many questions as they have provided answers. For example, the “standard” sort of xeroderma pigmentosum is chromosomally sensitive to ultraviolet light and to those chemical agents inducing ultraviolet-type DNA repair. But both it and the variant form have been reported to also be sensitive to the crosslinking agent mitomycin C in one study [18], implying a common step or steps in the repair of pyrimidine cyclobutane dimers and DNA crosslinks. However, just to complicate matters, another study of chromosomal aberration production in xeroderma pigmentosum cells had found them no more sensitive to mitomycin C than normal cells [50]. Similarly, Fanconi’s anemia cells, which are chromosomally sensitive to crosslinking agents, and appear to be defective in the “unhooking” of linked polynucleotide strands [15, 16, 49, 51], are reported to be chromosomally sensitive to ethyl methanesulfonate as well [29], and to be sensitive to ionizing radiation [7, 19, ]0], again implying overlapping repair systems. It seems certain that further study of chromosomal aberration production in repair deficient cells by agents inducing various DNA lesions will reveal even greater complexity in eukaryotic DNA repair systems and their role in chromosomal aberration production. Nevertheless, there seems hope, at least, that such studies may also ultimately lead to a complete understanding of the molecular mechanisms involved.


Ataxia Telangiectasia Xeroderma Pigmentosum Ataxia Telangiectasia Chromatid Aberration Aberration Yield 
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  1. 1.
    Auerbach, A. D., and S. R. Wolman, Susceptibility of Fanconi’s anemia fibroblasts to chromosome damage by carcinogens, Nature, 261 (1976) 494–496.PubMedCrossRefGoogle Scholar
  2. 2.
    Bender, M. A, J. S. Bedford, and J. B. Mitchell, Mechanisms of chromosomal aberration production. II. Aberrations induced by 5-bromodeoxyuridine and visible light, Mutat. Res., 20 (1973) 403–416.PubMedCrossRefGoogle Scholar
  3. 3.
    Bender, M. A, H. G. Griggs, and J. S. Bedford, Mechanisms of chromosomal aberration production. III. Chemicals and ionizing radiation, Mutat. Res., 23 (1974) 197–212.PubMedCrossRefGoogle Scholar
  4. 4.
    Bender, M. A, H. G. Griggs, and P. L. Walker, Mechanisms of chromosomal aberration production. I. Aberration induction by ultraviolet light, Mutat. Res., 20 (1973) 387–402.PubMedCrossRefGoogle Scholar
  5. 5.
    Bender, M. A, J. L. Ivett, and S. M. Jacobs, Chromosomal aberrations induced by ultraviolet light, in preparation.Google Scholar
  6. 6.
    Bender, M. A, J. M. Rary, and R. P. Kale, Mechanisms of chromosomal aberration production. IV. Chromosomal radiosensitivity in ataxia telangiectasia, in preparation.Google Scholar
  7. 7.
    Bigelow, S. B., J. M. Rary, and M. A Bender, G2 chromosomal radiosensitivity in Fanconi’s anemia, Mutat. Res., 63 (1979) 189–199.PubMedCrossRefGoogle Scholar
  8. 8.
    Cavalier-Smith, T., Palindromic base sequences and replication of eukaryote chromosome ends, Nature, 250 (1974) 467–470.PubMedCrossRefGoogle Scholar
  9. 9.
    Chadwick, K. H., and H. P. Leenhouts, The rejoining of DNA double-strand breaks and a model for the formation of chromosomal rearrangements, Intern. J. Radiat. Biol., 33 (1978) 517–529.CrossRefGoogle Scholar
  10. 10.
    Christensen, R. C., C. A. Tobias, and W. D. Taylor, Heavy-ion-induced single-and double-strand breaks in øx174 replicative form DNA, Intern. J. Radiat. Biol., 22 (1972) 457–477.CrossRefGoogle Scholar
  11. 11.
    Cory, P. M., and A. Cole, Double strand rejoining in mammalian DNA, Nature, 245 (1973) 100–101.Google Scholar
  12. 12.
    Dubinin, N. P., and U. N. Soyfer, Chromosome breakage and complete genic mutation production in molecular terms, Mutat. Res., 8 (1969) 353–365.PubMedCrossRefGoogle Scholar
  13. 13.
    Fornace, A. J., K. W. Kohn, and H. E. Kann, DNA single strand breaks during repair of UV damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum, Proc. Natl. Acad. Sci. (U.S.), 73 (1976) 39–43.CrossRefGoogle Scholar
  14. 14.
    Fornace, A. J., H. Nagasawa, and J. B. Little, Relationship of DNA repair and chromosome aberrations to potentially lethal damage repair in X-irradiated mammalian cells, This volume, p. 267.Google Scholar
  15. 15.
    Fujiwara, Y., and M. Tatsumi, Repair of mitomycin C damage to DNA in mammalian cells in Fanconi’s anemia cells, Biochem. Biophys. Res. Comm., 66 (1975) 592–598.PubMedCrossRefGoogle Scholar
  16. 16.
    Fujiwara, Y., M. Tatsumi, and M. S. Sasaki, Cross-link repair in human cells and its possible defect in Fanconi’s anemia cells, J. Mol. Biol., 113 (1977) 635–649.PubMedCrossRefGoogle Scholar
  17. 17.
    Griggs, H. G., and M. A Bender, Photoreactivation of ultraviolet-induced chromosomal aberrations, Science, 179 (1973) 86–88.PubMedCrossRefGoogle Scholar
  18. 18.
    Hartley-Asp, B., The influence of caffeine on the mitomycin C-induced chromosome aberration frequency in normal human and xeroderma pigmentosum cells, Mutat. Res., 49 (1978) 117–126.PubMedCrossRefGoogle Scholar
  19. 19.
    Higurachi, M., and P. E. Conen, In vitro chromosomal radio-sensitivity in Fanconi’s anemia, Blood, 38 (1971) 336–342.Google Scholar
  20. 20.
    Higurachi, M., and P. E. Conen, In vitro chromosomal radio-sensitivity in “chromosomal breakage syndromes,” Cancer, 32 (1973) 380–383.CrossRefGoogle Scholar
  21. 21.
    Ho, K. S. Y., Induction of DNA double-strand breaks by X-rays in a radiosensitive strain of the yeast Saccharomyces cerevisiae, Mutat. Res., 30 (1975) 327–334.PubMedCrossRefGoogle Scholar
  22. 22.
    Holmberg, M., Lack of synergistic effect between X-ray and UV irradiation on the frequency of chromosome aberrations in PHA-stimulated human lymphocytes in the G1 stage, Mutat. Res., 34 (1976) 141–148.PubMedCrossRefGoogle Scholar
  23. 23.
    Ikushima, T., and S. Wolff, UV-induced chromatid aberrations in cultured Chinese hamster cells after one, two or three rounds of DNA replication, Mutat. Res., 22 (1974) 193–201.PubMedCrossRefGoogle Scholar
  24. 24.
    Johnson, R. T., and P. N. Rao, Mammalian cell fusion: induction of premature chromosome consensation in interphase nuclei, Nature, 226 (1970) 717–722.PubMedCrossRefGoogle Scholar
  25. 25.
    Kelley, J. E. T., and M. A Bender, On the relationship between polynucleotide strand breakage and chromosome aberration production as a function of LET: I. Single strand/double strand break ratios; in preparation (1979).Google Scholar
  26. 26.
    Kihlman, B.A., Actions of Chemicals on Dividing Cells, Prentice-Hall, Englewood Cliffs, 1966.Google Scholar
  27. 27.
    Kihlman, B. A., Caffeine and Chromosomes, Elsevier, Amsterdam, 1977.Google Scholar
  28. 28.
    Krasin, F., and F. Hutchinson, Repair of DNA double-strand breaks in E. coli by recombination, Radiat. Res., 67 (1976) 534.Google Scholar
  29. 29.
    Latt, S. A., G. Stetten, L. A. Juergens, G. R. Buchanan, and P. S. Gerald, Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi’s anemia, Proc. Natl. Acad. Sci. (U.S.), 72 (1975) 4066–4070.CrossRefGoogle Scholar
  30. 30.
    Lea, D. E., Actions of Radiations on Living Cells, 2nd ed., Cambridge, 1955.Google Scholar
  31. 31.
    Lehman, A. R., and S. Stevens, The production and repair of double strand breaks in cells from normal humans and from patients with ataxia telangiectasia, Biochem. Biophys. Acta, 474 (1977) 49–60.PubMedGoogle Scholar
  32. 32.
    Lehman, A. R., S. Kirk-Bell, C. F. Arlett, M. C. Paterson, P. M. H. Lohman, E. A. DeWeerd-Kastelein and D. Bootsma, xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation, Proc. Natl. Acad. Sci. (U.S.), 72 (1975) 219–233.CrossRefGoogle Scholar
  33. 33.
    Maher, V. M., J. J. McCormick, P. L. Grover, and P. Sims, Effect of DNA repair on the cytotoxicity and mutagenicity of polycyclic hydrocarbon derivatives in normal and xeroderma pigmentosum human fibroblasts, Mutat. Res., 43 (1977) 117–138.PubMedCrossRefGoogle Scholar
  34. 34.
    Marshall, R. R., and D. Scott, The relationship between chromosome damage and cell killing in UV-irradiated normal and xeroderma pigmentosum cells, Mutat. Res., 36 (1976) 397–400.PubMedCrossRefGoogle Scholar
  35. 35.
    Muller, W. E. G., and R. K. Zahn, Bleomycin, an antibiotic that removes thymine from double-stranded DNA, Progr. Nucleic Acid Res. Mol. Biol. 20 (1977) 21–57.CrossRefGoogle Scholar
  36. 36.
    Natarajan, A. T., and G. Obe, Molecular mechanisms involved in the production of chromosomal aberrations. I. Utilization of Neurospora endonuclease for the study of aberration production in G2 stage of the cell cycle, Mutat. Res., 52 (1978) 137–149.PubMedCrossRefGoogle Scholar
  37. 37.
    Orr, T. V., and H. G. Griggs, Chromosomal aberrations resulting from UV exposures to G1 Xenopus cells, Photochem. Photobiol., 30 (1979) 363–368.PubMedCrossRefGoogle Scholar
  38. 38.
    Parrington, J. M., J. D. A. Delhanty, and H. P. Baden, Unscheduled DNA synthesis, UV-induced chromosome aberrations and SV40 transformation in cultured cells from xeroderma pigmentosum, Ann. Human Genet., 35 (1971) 149–160.CrossRefGoogle Scholar
  39. 39.
    Paterson, M. C., B. P. Smith, P. M. H. Lohman, A. K. Anderson, and L. Fishman, Defective excision repair of x-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts, Nature, 260 (1976) 444–447.PubMedCrossRefGoogle Scholar
  40. 40.
    Poon, R., T. A. Beerman, and I. H. Goldberg, Characterization of DNA strand breakage in vitro by the antitumor protein neocarzinostatin, Biochemistry, 16 (1977) 486–493.PubMedCrossRefGoogle Scholar
  41. 41.
    Rary, J. M., M. A Bender, and T. E. Kelly, Cytogenetic studies of ataxia telangiectasia, Am. J. Human Genet., 26 (1974) 70a.Google Scholar
  42. 42.
    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
  43. 43.
    Remsen, J. F., and P. A. Cerutti, Deficiency of gamma-ray excision repair in skin fibroblasts from patients with Fanconi’s anemia, Proc. Natl. Acad. Sci. (U.S.), 73 (1976) 2419–2423.CrossRefGoogle Scholar
  44. 44.
    Remsen, J. F., and P. A. Cerutti, Excision of gamma-ray induced thymine lesions by preparations from ataxia telangiectasia fibroblasts, Mutat. Res., 43 (1977) 139–146.PubMedCrossRefGoogle Scholar
  45. 45.
    Resnick, M. A., The repair of double-strand breaks in DNA: a model involving recombination, J. Theor. Biol., 59 (1976) 97–106.PubMedCrossRefGoogle Scholar
  46. 46.
    Resnick, M. A., and P. Martin, The repair of double-strand breaks in the nuclear DNA of Saccharomyces cerevisiae and its genetic control, Mol. Gen. Genet., 143 (1976) 110–129.CrossRefGoogle Scholar
  47. 47.
    Robbins, J. H., W. R. Lewis, and A. E. Miller, Xeroderma pigmentosum epidermal cells with normal UV-induced thymidine incorporation, J. Invest. Dermatol., 59 (1972) 5402–5408.CrossRefGoogle Scholar
  48. 48.
    Sasaki, M. S., DNA repair capacity and susceptibility to chromosome breakage in Xeroderma pigmentosum cells, Mutat. Res., 20 (1973) 291–293.PubMedCrossRefGoogle Scholar
  49. 49.
    Sasaki, M. S., Is Fanconi’s anemia defective in a process essential to the repair of DNA cross links? Nature, 257 (1975) 501–503.PubMedCrossRefGoogle Scholar
  50. 50.
    Sasaki, M. S., Cytogenetic evidence for the repair of DNA cross-links: its normal functioning in Xeroderma pigmentosum and its impairment in Fanconi’s anemia, Mutat. Res., 46 (1977) 152–153.Google Scholar
  51. 51.
    Sasaki, M. S., and A. Tonomura, A high susceptibility of Fanconi’s anemia to chromosome breakage by DNA cross-linking agents, Cancer Res., 33 (1973) 1829–1836.PubMedGoogle Scholar
  52. 52.
    Savage, J. R. K., Radiation-induced chromosomal aberrations in the plant Tradescantia: Dose-response curves. I. Preliminary considerations, Radiat. Bot., 15 (1975) 87–140.CrossRefGoogle Scholar
  53. 53.
    Schneider, E. L., R. R. Tice, and D. Kram, Bromodeoxyuridine-differential staining technique: a new approach to examining sister chromatid exchange and cell replication kinetics, In: Methods in Cell Biology, Vol. 20, D. M. Prescott (Ed.), Academic Press, New York, 1978, pp. 379–409.Google Scholar
  54. 54.
    Schuler, D., A. Kiss, and F. Fabian, Chromosomal pecularities and “in vitro” examinations in Fanconi’s anemia, Humangenetik, 7 (1969) 314–422.PubMedCrossRefGoogle Scholar
  55. 55.
    Setlow, R. B., and J. K. Setlow, Effects of radiation on polynucleotides, In: Annual Review of Biophysics and Bioengineering, M. F. Morales, W. A. Hagins, L. Stryer, and W. S. Yamamoto (Eds.), Vol. 1, Annual Reviews Inc., Palo Alto, Calif., 1972, pp. 293–346.Google Scholar
  56. 56.
    Stich, H. F., W. Stich, and R. H. C. San, Chromosome aberrations in xeroderma pigmentosum cells exposed to the carcinogens 4-nitroquinoline-1-oxide and N-methyl-N′-nitro-nitroso-guanidine, Proc. Soc. Exp. Biol. Med., 142 (1973) 1141–1144.PubMedGoogle Scholar
  57. 57.
    Taylor, A. M. R., Unrepaired DNA strand breaks in irradiated ataxia telangiectasia lymphocytes suggested from cytogenetic observations, Mutat. Res., 50 (1978) 407–418.PubMedCrossRefGoogle Scholar
  58. 58.
    Taylor, A. M. R., D. G. Harnden, C. F. Arlett, S. A. Harcourt, S. Stevens, and B. A. Bridges, Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity, Nature, 258 (1975) 427–429.PubMedCrossRefGoogle Scholar
  59. 59.
    Taylor, A. M. R., J. A. Metcalfe, J. M. Oxford, and D. G. Harnden, Is chromatid type damage in ataxia telangiectasia after irradiation at Go a consequence of defective repair? Nature, 260 (1976) 441–443.PubMedCrossRefGoogle Scholar
  60. 60.
    Taylor, J. H., Radioisotope studies on the structure of the chromosome, In: Radiation-Induced Chromosome Aberrations, S. Wolff (Ed.), Columbia University Press, New York, 1963.Google Scholar
  61. 61.
    Taylor, J. H., W. F. Haut, and J. Tung, Effects of fluorodeoxyuridine on DNA replication, chromosome breakage and reunion, Proc. Natl. Acad. Sci. (U.S.), 48 (1962) 190–198.CrossRefGoogle Scholar
  62. 62.
    Taylor, H. J., P. S. Woods, and W. L. Hughes, The organization and duplication of chromosomes as revealed by autoradiographic studies using tritium-labeled thymidine, Proc. Natl. Acad. Sci. (U.S.), 43 (1957) 122–128.CrossRefGoogle Scholar
  63. 63.
    Vincent, R. A., R. B. Sheridan, and P. C. Huang, DNA strand breakage repair in ataxia telangiectasia fibroblast-like cells, Mutat. Res., 33 (1975) 357–366.PubMedCrossRefGoogle Scholar
  64. 64.
    Wolff, S., The doubleness of the chromosome before DNA synthesis as revealed by combined x-ray and tritiated thymidine treatments, Radiat. Res., 14 (1961) 517–518.Google Scholar
  65. 65.
    Wolff, S., and P. Perry, Differential Giemsa staining of sister chromatids and the study of sister chromatid exchanges without autoradiography, Chromosoma, 48 (1974) 341–353.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Michael A. Bender
    • 1
  1. 1.Medical DepartmentBrookhaven National LaboratoryUptonUSA

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