Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Mar;69(3):457–462. doi: 10.1038/bjc.1994.83

Initial radiation-induced DNA damage in human tumour cell lines: a correlation with intrinsic cellular radiosensitivity.

J M Ruiz de Almodóvar 1, M I Núñez 1, T J McMillan 1, N Olea 1, C Mort 1, M Villalobos 1, V Pedraza 1, G G Steel 1
PMCID: PMC1968865  PMID: 8123473

Abstract

The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitivity was studied in human breast and bladder cancer cell lines. Cell survival was measured by monolayer colony-forming assay as appropriate and differences in radiosensitivity were seen (alpha-values ranged from 0.12 to 0.54). After pulsed-field gel electrophoresis (PFGE) the initial slopes of dose-response curves were biphasic with a flattening of the curves above 30 Gy. When the frequency of DNA dsb induction was assessed using a mathematical model based on the DNA fragment size distribution into the gel lane, we found a statistically significant relationship between the number of DNA dsb induced and the corresponding alpha-values and fraction surviving after 2Gy (P = 0.0049 and P = 0.0031 respectively). These results support the view that initial damage is a major determinant of cell radiosensitivity.

Full text

PDF
457

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chiu S. M., Friedman L. R., Oleinick N. L. Formation and repair of DNA-protein crosslinks in newly replicated DNA. Radiat Res. 1989 Dec;120(3):545–551. [PubMed] [Google Scholar]
  2. Contopoulou C. R., Cook V. E., Mortimer R. K. Analysis of DNA double strand breakage and repair using orthogonal field alternation gel electrophoresis. Yeast. 1987 Jun;3(2):71–76. doi: 10.1002/yea.320030203. [DOI] [PubMed] [Google Scholar]
  3. Cook V. E., Mortimer R. K. A quantitative model of DNA fragments generated by ionizing radiation, and possible experimental applications. Radiat Res. 1991 Jan;125(1):102–106. [PubMed] [Google Scholar]
  4. Deacon J., Peckham M. J., Steel G. G. The radioresponsiveness of human tumours and the initial slope of the cell survival curve. Radiother Oncol. 1984 Dec;2(4):317–323. doi: 10.1016/s0167-8140(84)80074-2. [DOI] [PubMed] [Google Scholar]
  5. Fertil B., Malaise E. P. Inherent cellular radiosensitivity as a basic concept for human tumor radiotherapy. Int J Radiat Oncol Biol Phys. 1981 May;7(5):621–629. doi: 10.1016/0360-3016(81)90377-1. [DOI] [PubMed] [Google Scholar]
  6. Iliakis G., Okayasu R. The level of induced DNA double-strand breaks does not correlate with cell killing in X-irradiated mitotic and G1-phase CHO cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1988 Mar;53(3):395–404. doi: 10.1080/09553008814552531. [DOI] [PubMed] [Google Scholar]
  7. Kelland L. R., Steel G. G. Differences in radiation response among human cervix carcinoma cell lines. Radiother Oncol. 1988 Nov;13(3):225–232. doi: 10.1016/0167-8140(88)90059-x. [DOI] [PubMed] [Google Scholar]
  8. Keydar I., Chen L., Karby S., Weiss F. R., Delarea J., Radu M., Chaitcik S., Brenner H. J. Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer. 1979 May;15(5):659–670. doi: 10.1016/0014-2964(79)90139-7. [DOI] [PubMed] [Google Scholar]
  9. Lippman M., Bolan G., Huff K. The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res. 1976 Dec;36(12):4595–4601. [PubMed] [Google Scholar]
  10. Masters J. R., Hepburn P. J., Walker L., Highman W. J., Trejdosiewicz L. K., Povey S., Parkar M., Hill B. T., Riddle P. R., Franks L. M. Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines. Cancer Res. 1986 Jul;46(7):3630–3636. [PubMed] [Google Scholar]
  11. Olive P. L. DNA organization affects cellular radiosensitivity and detection of initial DNA strand breaks. Int J Radiat Biol. 1992 Oct;62(4):389–396. doi: 10.1080/09553009214552261. [DOI] [PubMed] [Google Scholar]
  12. Peacock J. H., Eady J. J., Edwards S. M., McMillan T. J., Steel G. G. The intrinsic alpha/beta ratio for human tumour cells: is it a constant? Int J Radiat Biol. 1992 Apr;61(4):479–487. doi: 10.1080/09553009214551241. [DOI] [PubMed] [Google Scholar]
  13. Radford I. R. Evidence for a general relationship between the induced level of DNA double-strand breakage and cell-killing after X-irradiation of mammalian cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Apr;49(4):611–620. doi: 10.1080/09553008514552861. [DOI] [PubMed] [Google Scholar]
  14. Schwartz J. L., Vaughan A. T. Association among DNA/chromosome break rejoining rates, chromatin structure alterations, and radiation sensitivity in human tumor cell lines. Cancer Res. 1989 Sep 15;49(18):5054–5057. [PubMed] [Google Scholar]
  15. Soto A. M., Murai J. T., Siiteri P. K., Sonnenschein C. Control of cell proliferation: evidence for negative control on estrogen-sensitive T47D human breast cancer cells. Cancer Res. 1986 May;46(5):2271–2275. [PubMed] [Google Scholar]
  16. Soto A. M., Sonnenschein C. The role of estrogens on the proliferation of human breast tumor cells (MCF-7). J Steroid Biochem. 1985 Jul;23(1):87–94. doi: 10.1016/0022-4731(85)90265-1. [DOI] [PubMed] [Google Scholar]
  17. Soule H. D., Vazguez J., Long A., Albert S., Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 1973 Nov;51(5):1409–1416. doi: 10.1093/jnci/51.5.1409. [DOI] [PubMed] [Google Scholar]
  18. Steel G. G., McMillan T. J., Peacock J. H. The radiobiology of human cells and tissues. In vitro radiosensitivity. The picture has changed in the 1980s. Int J Radiat Biol. 1989 Nov;56(5):525–537. doi: 10.1080/09553008914551691. [DOI] [PubMed] [Google Scholar]
  19. Whitaker S. J., McMillan T. J. Oxygen effect for DNA double-strand break induction determined by pulsed-field gel electrophoresis. Int J Radiat Biol. 1992 Jan;61(1):29–41. doi: 10.1080/09553009214550591. [DOI] [PubMed] [Google Scholar]
  20. del Moral R., Ruiz de Almodóvar J. M., Fernández J. C., López-González J. D., Villalba J., Olea N., Pedraza V. Relationship between proliferative activity and cellular hormono-dependence in the MCF-7 breast cancer cell line. Rev Esp Fisiol. 1990 Sep;46(3):247–253. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES