Summary
The induction of collateral radioresistance after the development of cisplatin resistance is a well-documented phenomenon; however, the exact processes that are responsible for the cisplatin-induced radioresistance remain to be elucidated. There was no obvious difference in the level of radiation-induced DNA double strand breaks (DSBs), in DSB rejoining rates, or the level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in the cisplatin- and radiation-sensitive 2780/WT and cisplatin-resistant 2780/CP cell lines. However, there was a significantly (P< 0.01) lower level of DSB misrejoining activity within nuclear protein extracts derived from the cisplatin-and radiation-sensitive 2780/WT and OAW42/WT tumour cell lines than in similar extracts from their cisplatin- (and radiation-) resistant 2780/CP and OAW42/CP counterparts. All of the DSB misrejoining events involved deletions of between 134 and 444 bp that arose through illegitimate recombination at short repetitive sequences, such as those that arise through non-homologous repair (NHR). These data further support the notion that the radiosensitivity of DSB repair proficient human tumour cell lines may be partly determined by the predisposition of these cell lines to activate non-conservative DSB rejoining pathways. Furthermore, our data suggest that the induction of acquired cisplatin resistance is associated with a two- to threefold decrease in the activity of a non-conservative DSB rejoining mechanism that appears to be a manifestation of NHR.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Bill, C. A., Yu, Y., Miselis, N. R., Little, J. B. & Nickoloff, J. A. (1997). A role for p53 in DNA end rejoining by human cell extracts. Mutant Res 385: 21–29.
Britten, R. A., Warenius, H. M., Masters, J. R. W. & Peacock, J. H. (1993). The differential induction of collateral resistance to 62.5 MeV (p→Be+) neutrons and 4 MeV photons by exposure to cis-platinum. Int J Radiat Oncol Biol Phys 26: 837–843.
Britten, R. A., Warenius, H. M., Carraway, A. V. & Murray, D. (1994). Differential modulation of radiosensitivity following induction of cis-platinum resistance in radiation-sensitive and radiation-resistant human tumor cells. Radiat Oncol Invest 2: 25–31.
Britten, R. A., Liu, D., Kuny, S. & Allalunis-Turner, M. J. (1997). Differential level of DSB repair fidelity effected by nuclear protein extracts derived from radiosensitive and radioresistant human tumour cells. Br J Cancer 76: 1440–1447.
Bryant, P. E. & Liu, N. (1994). Responses of radiosensitive repair-proficient cell lines to restriction endonucleases. Int J Radiat Biol 66: 597–601.
Cizeau, J., Decoville, M., Leng, M. & Locker, D. (1996). Large deletions in the whitegene of Drosophila melanogasterby the antitumoral drug cis-dichlorodiammineplatinum (II): influence of non-homologous recombination. Mutat Res 356: 197–202.
Cox, R., Masson, W. K., Debenham, P. G. & Webb, M. B. T. (1984). The use of recombinant DNA plasmids for the determination of DNA-repair and recombination in cultured mammalian cells. Br J Cancer 49(suppl. VI): 67–72.
Fishel, R., Derbyshire, M. K., Moore, S. P. & Young, C. S. H. (1991). Biochemical studies of homologous and nonhomologous recombination in human cells. Biochimie 73: 257–267.
Ganesh, A., North, P. & Thacker, J. (1993). Repair and misrepair of site-specific DNA double-strand breaks by human cell extracts. Mutat Res 299: 251–259.
Giaccia, A., Weinstein, R., Hu, J. & Stomato, T. D. (1985). Cell cycle repair of double-strand DNA breaks in a gamma-ray-sensitive Chinese hamster cell. Somat Cell Mol Genet 11: 485–491.
Hida, T., Ueda, R., Takahashi, T., Watanabe, H., Kato, T., Suyama, M., Sugiura, T., Ariyoshi, Y. & Takahashi, T. (1989). Chemosensitivity and radiosensitivity of small cell lung cancer cell lines studied by a newly developed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) hybrid assay. Cancer Res 49: 4785–4790.
Kirchgessner, C. U., Patil, C. K., Evans, J. W., Cuomo, C. A., Fried, L. M., Carter, T., Oettinger, M. A. & Brown, J. M. (1995). DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267: 1178–1183.
Lambin, P., Coco-Martin, J., Legal, J. D., Begg, A. C., Parmentier, C., Joiner, M. C. & Malaise, E. P. (1994). Intrinsic radiosensitivity and chromosome aberration analysis using fluorescence in situ hybridization in cells of two human tumor cell lines. Radiat Res 138: S40–43.
Lees-Miller, S. P., Godbout, R., Chan, D. W., Weinfeld, M., Day, R. S., Barron, G. M. & Allalunis-Turner, J. (1995). Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 267: 1183–1185.
Liu, N. & Bryant, P. E. (1993). Response of ataxia telangiectasia cells to restriction endonuclease induced DNA double-strand breaks. I. Cytogenetic characterization. Mutagenesis 8: 503–510.
Lou, C-M, Tang, W., Mekeel, K. L., DeFrank, J. S., Rani Anné, P. & Powell, S. N. (1996). High frequency and error-prone DNA recombination in ataxia telangiectasia cell lines. J Biol Chem 271: 4497–4503.
Louie, K. G., Behrens, B. C., Kinsella, T. J., Hamilton, T. C., Grotzinger, K. R., McKoy, W. M., Winker, M. A. & Ozols, R. F. (1985). Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cell lines and their modification by buthionine sulfoximine. Cancer Res 45: 2110–2115.
McKay, M. J. & Kefford, R. F. (1995). The spectrum of in vitroradiosensitivity in four human melanoma cell lines is not accounted for by differential induction or rejoining of DNA double strand breaks. Int J Radiat Oncol Biol Phys 31: 345–352.
Murray, D., Simpson, R., Rosenberg, E., Carraway, A. & Britten, R. (1994). Correlation between γ-ray induced DNA double-strand breakage and cell killing after biologically relevant doses: analysis by pulsed-field gel electrophoresis. Int J Radiat Biol 65: 419–426.
Olive, P. L., Banáth, J. P. & MacPhail, H. S. (1994). Lack of a correlation between radiosensitivity and DNA double-strand break induction or rejoining in six human tumor cell lines. Cancer Res 54: 3939–3946.
Powell, S. & McMillan, T. J. (1991). Clonal variation of DNA repair in a human glioma cell line. Radiother Oncol 21: 225–232.
Powell, S. N. & McMillan, T. J. (1994). The repair fidelity of restriction enzyme-induced double strand breaks in plasmid DNA correlates with radioresistance in human tumor cell lines. Int J Radiat Oncol Biol Phys 29: 1035–1040.
Powell, S. N., Whitaker, S. J., Edwards, S. M. & McMillan, T. J. (1992). A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line. Br J Cancer 65: 798–802.
Powell, S. N., Whitaker, S., Peacock, J. H. & McMillan, T. J. (1993). Ataxia telangiectasia: an investigation of the repair defect in the cell line AT5BIVA by plasmid reconstitution. Mutat Res 294: 9–20.
Russell, N. S., Arlett, C. F., Bartelink, H. & Begg, A. C. (1995). Use of fluorescence in situ hybridization to determine the relationship between chromosome aberrations and cell survival in eight human fibroblast strains. Int J Radiat Biol 68: 185–196.
Sasai, K., Evans, J. W., Kovacs, M. S. & Brown, J. M. (1994). Prediction of human cell radiosensitivity: comparison of clonogenic assay with chromosome aberrations scored with premature chromosome condensation with fluorescence in situ hybridization. Int J Radiat Oncol Biol Phys 30: 1127–1132.
Schwartz, J. L. & Vaughan, A. T. M. (1989). Association among DNA/chromosome break rejoining rates, chromatin structure alterations, and radiation sensitivity in human tumor cell lines. Cancer Res 49: 5054–5057.
Smeets, MFMA, Mooren, E. H. M. & Begg, A. C. (1993). Radiation-induced DNA damage and repair in radiosensitive and radioresistant human tumour cells measured by field inversion gel electrophoresis. Int J Radiat Biol 63: 703–713.
Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P. & Jeggo, P. A. (1994). Ku80: product of XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 265: 1442–1445.
Thacker, J. & Ganesh, A. N. (1990). DNA-break repair, radioresistance of DNA synthesis, and camptothecin sensitivity in the radiation-sensitive irsmutants: comparisons to ataxia-telangiectasia cells. Mutat Res 235: 49–58.
Thacker, J., Chalk, J., Ganesh, A. & North, P. (1992). A mechanism for deletion formation in DNA by human cell extracts: the involvement of short sequence repeats. Nucleic Acids Res 20: 6183–6188.
Turchi, J. J., Patrick, S. M. & Henkels, K. M. (1997). Mechanisms of DNA-dependent protein kinase inhibition by cis-diamminedichloroplatinum(II)-damaged DNA. Biochemistry 36: 7586–7593.
Twentyman, P. R., Wright, K. A. & Rhodes, T. (1991). Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin. Int J Radiat Oncol Biol Phys 20: 217–220.
Weng, G. & Nickoloff, J. (1997). Conversion on opposite sides of a double-strand break can be mediated by two mismatch repair tracts. Proc Am Assoc Cancer Res 38: A2399
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Britten, R., Kuny, S. & Perdue, S. Modification of non-conservative double-strand break (DSB) rejoining activity after the induction of cisplatin resistance in human tumour cells. Br J Cancer 79, 843–849 (1999). https://doi.org/10.1038/sj.bjc.6690135
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690135