Skip to main content
SpringerLink
Log in

Modulation of the effect of camptothecin in x-irradiated L5178Y-R and L5178Y-S cells by benzamide

  • Original Paper
  • Published:
Radiation and Environmental Biophysics Aims and scope Submit manuscript

Abstract

The L5178Y (LY) murine lymphoma subline, LY-R, is more radioresistant and more sensitive to camptothecin (CPT, inhibitor of topisomerase I) than the second subline used in our investigation, LY-S. Post-irradiation treatment with 3 μM CPT enhanced the radiosensitivity of LY-S cells (D0 decrease from 0.52 to 0.34 Gy), but did not change it in LY-R cells. Treatment with 2 mM benzamide [BZ, inhibitor of poly(ADP-ribosylation) before x-rays and CPT increased the radiosensitivity of LY-R cells (D0 decrease from 1.15 to 0.52) without further modification of radiosensitivity of LY-S cells. Activity of topoisomerase I was diminished 10 min after x-irradiation (5 Gy) in LY-S, but not in LY-R cells. The data on DNA damage (fluorescent halo or comet assays) showed that the ultimate fate of the cells did not depend on the DNA damage pattern estimated immediately after treatment (e.g. the damage was greater in x-rays plus CPT than in BZ plus x-rays plus CPT treated LY-R cells, although the radiosensitivity was less). Aphidicolin (inhibitor of DNA polymerases α and δ) applied concomitantly with CPT in cells not pretreated with BZ prevented the increase in DNA damage in LY-R cells, but was without effect in LY-S cells. Taking into account the differential inhibition by x-rays of DNA synthesis in LY sublines and its reversion by BZ in LY-S but not in LY-R cells, we conclude that the pattern of DNA damage observed by the methods applied depended on the status of DNA replication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mattern MR, Hofmann GA, McCabe FL, Johnson RK (1991) Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK & F104864). Cancer Res 51: 5813–5816

    Google Scholar 

  2. Boothman DA, Wang W, Schea RA, Burrows HL, Strickfaden S, Owens JK (1992) Posttreatment exposure to camptotheein enhances the lethal effects of X-rays on radioresistant human malignant melanoma cells. Int J Radiat Oncol Biol Phys 24: 939–948

    Google Scholar 

  3. Kim JH, Kim SH, Kolozsvary A, Khil MS (1992) Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma cells in vivo by topotecan, an inhibitor of DNA topoisomerase I. Int J Radiat Oncol Biol Phys 22: 515–518

    Google Scholar 

  4. Hennequin C, Giocanti N, Balosso J, Favaudon V (1994) Interaction of ionizing radiation with the topoisomerase I poison camptothecin in growing V-79 and HeLa cells. Cancer Res 54: 1720–1728

    Google Scholar 

  5. Ng CE, Bussey AM, Raaphorst GP (1994) Inhibition of potentially lethal and sublethal damage repair by camptothecin and etoposide in human melanoma cell lines. Int J Radiat Biol 66: 49–57

    Article  Google Scholar 

  6. Roffler SR, Chan J, Yeh MY (1994) Potentiation of radioimmunotherapy by inhibition of topoisomerase I. Cancer Res 54: 1276–1285

    Google Scholar 

  7. Skov K, Zhou H, Marples B (1994) The effect of two topoisomerase inhibitors on low-dose hypersensitivity and increased radioresistance in Chinese hamster V79 cells. Radiat Res 138: S117-S120

    Article  Google Scholar 

  8. Szumiel I, Buraczewska I, Gradzka I, Gasińska A (1995) Effects of topoisomerase I-targeted drugs on radiation response of L5178Y sublines differentially radiation and drug sensitive. Int J Radiat Biol 67: 441–448

    Article  Google Scholar 

  9. Boothman DA, Fukunaga N, Wang M (1994) Down-regulation of topoisomerase I in mammalian cells following ionizing radiation. Cancer Res 54: 4618–4626

    Google Scholar 

  10. Szumiel I (1979) Response of two strains of L5178Y cells to cis-dichlorobis(cyclopentylamine) platinum II. Chem Biol Interact 24: 51–72

    Article  Google Scholar 

  11. Kowalska-Loth B, Staroń K, Buraczewska I, Szumiel I, Kapiszewska M, Lange CS (1993) Reduced sensitivity to camptothecin of topoisomerase I from a L5178Y mouse lymphoma subline sensitive to X-radiation. Biochim Biophys Acta 1172: 117–123

    Google Scholar 

  12. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184–191

    Article  Google Scholar 

  13. Green MHL, Lowe JE, Harcourt SA, Akinluyi P, Rowe T, Cole J, Anstey AV, Arlett CF (1992) UV-C sensitivity of unstimulatd and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay: a potential diagnostic technique. Mutat Res 273: 137–144

    Google Scholar 

  14. Fairbairn DW, Olive P, O’Neill KL (1995) The comet assay: a comprehensive review. Mutat Res 339: 37–59

    Google Scholar 

  15. Kapiszewska M, Szumiel I, Lange CS (1992) Damage at two levels of DNA folding measured by fluorescent halo technique in X-irradiated L5178Y-R and L5178Y-S cells. I. Initial lesions. Radiat Environ Biophys 31: 311–322

    Article  Google Scholar 

  16. Roti Roti JL, Wright WD (1987) Visualization of DNA loops in nucleoids from HeLa cells: assay for DNA damage and repair. Cytometry 8: 461–467

    Article  Google Scholar 

  17. Szumiel I, Wlodek D, Zernik M, Szabo G (1983) Contribution of ADP-ribosylation to cellular recovery of L5178Y-R and L5178Y-S lymphoblasts. In: Biological effects of low-level radiation, International Atomic Energy Agency, Vienna, pp 427–434

    Google Scholar 

  18. Staroń K, Kowalska-Loth B, Ząbek J, Czerwiński RM, Nieznański K, Szumiel I (1995) Topoisomerase I is differently phosphorylated in two sublines of L5178Y mouse lymphoma cells. Biochim Biophys Acta 1260: 35–42

    Google Scholar 

  19. Staroń K, Kowalska-Loth B, Nieznański K, Szumiel I (1996) Phosphorylation of topoisomerase I in L5178Y-S cells is associated with poly(ADP-ribose) metabolism. Carcinogenesis 17:383–388

    Article  Google Scholar 

  20. Kleczkowska HE, Szumiel I, Althaus FR (1990) Differential poly (ADP-ribose) metabolism in repair-proficient and repair-deficient murine lymphoma cells. Mutat Res 235: 93–99

    Google Scholar 

  21. Wlodek D, Hittelman WN (1987) The repair of double strand breaks correlates with radiosensitivity of L5178Y-R and L5178Y-S cells. Radiat Res 112: 146–155

    Article  Google Scholar 

  22. Wlodek D, Hittelman WN (1988) The relationship of DNA and chromosome damage to the survival of synchronized X-irradiated L5178Y cells. I. Initial damage. Radiat Res 115: 550–565

    Article  Google Scholar 

  23. Wlodek D, Hittelman WN (1988) The relationship of DNA and chromosome damage to the survival of synchronized X-irradiated L5178Y cells. H. Repair. Radiat Res 115: 566–575

    Article  Google Scholar 

  24. Zhang H, D’Arpa P, Liu LF (1990) A model for tumor cell killing by topoisomerase poisons. Cancer Cells 2: 23–27

    Google Scholar 

  25. Ryan AJ, Squires S, Strutt HL, Johnson RT (1991) Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. Nucleic Acids Res 19: 3295–3300

    Article  Google Scholar 

  26. McKelvey-Martin VJ, Green MHL, Schmezer P, Pool-Zobel BL, De Meo MP, Collins A (1993) The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res 288: 47–63

    Google Scholar 

  27. Lebkowski JS, Laemmli UK (1982) Evidence for two levels of DNA folding in histone depleted HeLa interphase nuclei. J Mol Biol 156: 309–324

    Article  Google Scholar 

  28. Berezney R (1991) The nuclear matrix: a heuristic model for investigating genomic organization and function in the cell nucleus. J Cell Biochem 47: 109–123

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiobiology, Institute of Nuclear Chemistry and Technology, Dorodna 16, PL-03-195, Warszawa, Poland

    Iwona Grądzka, Teresa Iwaneńko, Marcin Kruszewski & Irena Szumiel

  2. United Arab Emirates, University of United Arab Emirates, Al-Ain

    Maria Kapiszewska

  3. State University of New York Health Science Center at Brooklyn, 11203, Brooklyn, NY, USA

    Christopher S. Lange

  4. Institute of Chemical Physics, 117977, Moscow W334, Russia

    Georgij Afanasjev

Authors
  1. Iwona Grądzka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teresa Iwaneńko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcin Kruszewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irena Szumiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Kapiszewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christopher S. Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Georgij Afanasjev
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grądzka, I., Iwaneńko, T., Kruszewski, M. et al. Modulation of the effect of camptothecin in x-irradiated L5178Y-R and L5178Y-S cells by benzamide. Radiat Environ Biophys 35, 185–191 (1996). https://doi.org/10.1007/s004110050029

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s004110050029

Keywords

Search

Navigation