Effects of 3-Aminobenzamide on Cell-Cycle Traverse and Viability of Human Cells Exposed to Agents which Induce DNA Strand-Breakage

  • Paul J. Smith
  • Catherine O. Anderson
  • Steven H. Chambers
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

There is evidence that poly(ADP-ribosyl)ation, in response to DNA damage (review [1]), permits changes in chromatin structure [2] which may facilitate the activity of repair enzymes [3] and become a major factor in the control of cell-cycle traverse [4]. This paper explores the role of chromatin structure and poly(ADP-ribosyl)ation (using the inhibitor, 3-aminobenzamide; 3AB; [5]) in the responses of human cells to either a DNA specific ligand (Hoechst dye 33341; Ho33342) or X-radiation. Cells derived from an ataxia telangiectasia (A-T) patient have been included in the study to provide a hypersensitive control (reviews [6, 7]) in which anomalous cell survival and cell-cycle responses [8–10] to radiation may reflect a primary defect in chromatin structure [11, 12].

Keywords

Toxicity Filtration Albumin EDTA Argon 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Shall S (1982) ADP-ribose in DNA repair. In: Hayaishi O, Ueda K (eds) ADP-ribosylation reactions. Academic Press, London New York, p 472Google Scholar
  2. 2.
    Poirer GC, De Murcia G, Jongstra-Billen J, Niedergang C, Mandel P (1982) Poly(ADP-ribosyl)-ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci USA 79:3423–3427CrossRefGoogle Scholar
  3. 3.
    Creissen D, Shall S (1982) Regulation of DNA ligase activity by poly(ADP-ribose). Nature (London) 296:271–272CrossRefGoogle Scholar
  4. 4.
    Rowley R, Zorch M, Leeper DB (1984) Effect of caffeine on radiation — induced mitotic delay: delayed expression of G2 arrest. Radiat Res 97:178–185PubMedCrossRefGoogle Scholar
  5. 5.
    Purnell MR, Whish WJD (1980) Novel inhibitors of poly(ADP-ribose) synthetase. Biochem J 185:775–777PubMedGoogle Scholar
  6. 6.
    Paterson MC, Smith PJ (1979) Ataxia telangiectasia: an inherited human disorder involving hypersensitivity to ionizing radiation and related DNA-damaging chemicals. Annu Rev Genet 13:291–318PubMedCrossRefGoogle Scholar
  7. 7.
    Bridges BA, Harnden DG (1982) Ataxia-telangiectasia — a cellular and molecular link between cancer, neuropathology and immune deficiency. Wiley, ChichesterGoogle Scholar
  8. 8.
    Zampetti-Bosseler F, Scott D (1981) Cell death, chromosome damage and mitotic delay in normal human, ataxia telangiectasia and retinoblastoma fibroblasts after X-radiation. Int J Radiat Biol 39:547–558CrossRefGoogle Scholar
  9. 9.
    Imray FP, Kidson C (1983) Perturbations of cell-cycle progression in gamma-irradiated ataxia telangiectasia and Huntington’s disease cells detected by DNA flow cytometric analysis. Mutat Res 112:369–382PubMedGoogle Scholar
  10. 10.
    Ford MD, Martin L, Lavin MF (1984) The effects of ionizing radiation on cell cycle progression in ataxia telangiectasia. Mutat Res 125:115–122PubMedCrossRefGoogle Scholar
  11. 11.
    Painter RB, Young BR (1980) Radiosensitivity in ataxia telangiectasia: A new explanation. Proc Natl Acad Sci USA 77:7315–7317PubMedCrossRefGoogle Scholar
  12. 12.
    Jaspers NGJ, de Wit J, Regulski MR, Bootsma D (1982) Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents. Cancer Res 42:335–341PubMedGoogle Scholar
  13. 13.
    Igo-Kemenes T, Horz W, Zachau HG (1982) Chromatin. Annu Rev Biochem 51:89–121PubMedCrossRefGoogle Scholar
  14. 14.
    Darzynkiewicz Z (1979) Acridine orange as a molecular probe in studies of nucleic acids in situ. In: Melamed MR, Mullaney PF, Mendelsohn ML (eds) Flow cytometry and sorting. Wiley, New York, p 285Google Scholar
  15. 15.
    Latt SA (1979) Fluorescent probes of DNA microstructure and synthesis. In: Melamed MR, Mullaney PF, Mendelsohn ML (eds) Flow cytometry and sorting. Wiley, New York, p 139Google Scholar
  16. 16.
    Durand RE, Olive PL (1982) Cytotoxicity mutagenicity and DNA damage by Hoechst 33342. J Histochem Cytochem 30:111–116PubMedCrossRefGoogle Scholar
  17. 17.
    Smith PJ, Anderson CO (1984) Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative. Int J Radiat Biol 46:331–344CrossRefGoogle Scholar
  18. 18.
    Smith PJ (1984) Relationship between a chromatin anomaly in ataxia telangiectasia cells and enhanced sensitivity to DNA damage. Carcinogenesis 5:1345–1350PubMedCrossRefGoogle Scholar
  19. 19.
    Ganesan AK, Smith CA, Van Zeeland AA (1981) Measurement of the pyrimidine dimer content in DNA in permeabilized bacterial or mammalian cells with endonuclease V of bacteriophage T4. In: Friedberg EC, Hanawalt PC (eds) DNA repair. A laboratory manual of research techniques, vol I. Marcel Dekker, New York, p 89Google Scholar
  20. 20.
    Birnboim HC, Jevcak JJ (1981) Fluorometric method for rapid detection of DNA strand-breaks in human white blood cells produced by low doses of radiation. Cancer Res 41:1889–1892PubMedGoogle Scholar
  21. 21.
    Kanter PM, Schwartz HS (1982) A fluorescence enhancement assay for cellular DNA damage. Mol Pharmacol 22:145–151PubMedGoogle Scholar
  22. 22.
    Smith PJ, Paterson MC (1983) Effect of aphidicolin on de novo DNA synthesis, DNA repair and cytotoxicity in gamma-irradiated human fibroblasts: Implications for the enhanced radio-sensitivity in ataxia telangiectasia. Biochim Biophys Acta 739:17–26PubMedGoogle Scholar
  23. 23.
    Zwelling LA, Kerrigan D, Mattern MR (1983) Ataxia-telangiectasia cells are not uniformly deficient in poly(ADP-ribose) synthesis following X-irradiation. Mutat Res 120:69–78PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • Paul J. Smith
  • Catherine O. Anderson
  • Steven H. Chambers
    • 1
  1. 1.MRC Clinical Oncology and Radiotherapeutics UnitCambridgeGreat Britain

Personalised recommendations