DNA DSB induction and rejoining in V79 cells irradiated with light ions: a constant field gel electrophoresis study.

PURPOSE To study the induction and the time-course of rejoining of DNA double strand breaks (DSB) in V79 cells irradiated with light ions with different linear energy transfer (LET). MATERIALS AND METHODS V79 cells were irradiated in monolayer with monoenergetic proton, deuteron, helium-3 or helium-4 ion beams, each at two different energy values. Gamma rays were used as reference radiation. DSB have been measured by constant field gel electrophoresis (CFGE). RESULTS The initial yield depended little on the particle type and LET. The amount of DSB left unrejoined for up to 2 h incubation time could be roughly described by a decreasing exponential function with a final plateau, although more complex functions cannot be excluded. Radiation quality had little effect on the rejoining rate but affected the plateau. The amount of residual DSB after 2 h was higher for densely than for sparsely ionizing radiation, and for the same particle was dependent on LET. The corresponding RBE ranged from 1.8 to 6.0. CONCLUSIONS The results support the hypothesis that complex, less reparable DSB are induced in higher proportion by light ions with respect to gamma-rays and that, for the same ion, increasing LET leads to an increase in this proportion.

[1]  J. Arrand,et al.  Relative contributions of levels of initial DNA damage and repair of double strand breaks to the ionizing radiation-sensitive phenotype of the Chinese hamster cell mutant, XR-V15B. Part I. X-rays. , 1993, International journal of radiation biology.

[2]  F Ianzini,et al.  RBE-LET relationships for cell inactivation and mutation induced by low energy protons in V79 cells: further results at the LNL facility. , 1998, International journal of radiation biology.

[3]  K M Prise,et al.  Use of radiation quality as a probe for DNA lesion complexity. , 1994, International journal of radiation biology.

[4]  F Ianzini,et al.  Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. III. Initial yield of DNA double-strand breaks in V79 cells. , 1992, International journal of radiation biology.

[5]  B. Vojnovic,et al.  The irradiation of V79 mammalian cells by protons with energies below 2 MeV. Part I: Experimental arrangement and measurements of cell survival. , 1989, International journal of radiation biology.

[6]  D T Goodhead,et al.  Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. , 1994, International Journal of Radiation Biology.

[7]  J. Dahm-Daphi,et al.  Rejoining of DNA double-strand breaks in X-irradiated CHO cells studied by constant- and graded-field gel electrophoresis. , 1996, International journal of radiation biology.

[8]  R. Mortimer,et al.  A quantitative model of DNA fragments generated by ionizing radiation, and possible experimental applications. , 1991, Radiation research.

[9]  J. Lett,et al.  Damage to cellular DNA from particulate radiations, the efficacy of its processing and the radiosensitivity of mammalian cells , 1992, Radiation and environmental biophysics.

[10]  M. Flentje,et al.  DNA double-strand breaks in mammalian cells exposed to Á-rays and very heavy ions , 1998 .

[11]  E. Grusell,et al.  Rejoining of DNA double-strand breaks induced by accelerated nitrogen ions. , 1996, International journal of radiation biology.

[12]  F Ballarini,et al.  Modelling radiation-induced biological lesions: from initial energy depositions to chromosome aberrations , 1999, Radiation and environmental biophysics.

[13]  Detlef Blöcher,et al.  DNA Double-strand Break Repair Determines the RBE of α-particles , 1988 .

[14]  B. Rydberg,et al.  Clusters of DNA damage induced by ionizing radiation: formation of short DNA fragments. II. Experimental detection. , 1996, Radiation research.

[15]  M. Löbrich,et al.  Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  F Ianzini,et al.  DNA double-strand breaks induced by low energy protons in V79 cells. , 1994, International journal of radiation biology.

[17]  M. Löbrich,et al.  Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts. , 1998, Radiation research.

[18]  M. Frankenberg-Schwager,et al.  Evidence for DNA double-strand breaks as the critical lesions in yeast cells irradiated with sparsely or densely ionizing radiation under oxic or anoxic conditions. , 1981, Radiation research.

[19]  D T Goodhead,et al.  Molecular and cell models of biological effects of heavy ion radiation , 1995, Radiation and environmental biophysics.

[20]  R. Weichselbaum,et al.  Radiation-induced DNA double-strand break frequencies in human squamous cell carcinoma cell lines of different radiation sensitivities. , 1991, International journal of radiation biology.

[21]  M. Löbrich,et al.  Non-random distribution of DNA double-strand breaks induced by particle irradiation. , 1996, International journal of radiation biology.

[22]  G. Taucher‐Scholz,et al.  DNA strand break induction and rejoining and cellular recovery in mammalian cells after heavy-ion irradiation. , 1993, Radiation research.

[23]  I. Radford The level of induced DNA double-strand breakage correlates with cell killing after X-irradiation. , 1985, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[24]  L. Milas,et al.  Radioprotection of cultured mammalian cells by the aminothiols WR-1065 and WR-255591: correlation between protection against DNA double-strand breaks and cell killing after gamma radiation. , 1989, Radiation research.

[25]  G. Moschini,et al.  RBE-LET relationship for the survival of V79 cells irradiated with low energy protons. , 1989, International journal of radiation biology.

[26]  K. Prise,et al.  DNA double-strand break distributions in X-ray and alpha-particle irradiated V79 cells: evidence for non-random breakage. , 1997, International journal of radiation biology.

[27]  D Blöcher,et al.  In CHEF electrophoresis a linear induction of dsb corresponds to a nonlinear fraction of extracted DNA with dose. , 1990, International journal of radiation biology.

[28]  E. Sideris,et al.  Biological effectiveness of low energy protons. I. Survival of Chinese hamster cells. , 1986, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[29]  H. J. Brede,et al.  Induction of DNA double-strand breaks by 1H and 4He lons in primary human skin fibroblasts in the LET range of 8 to 124 keV/microm. , 1999, Radiation research.

[30]  B. Stenerlöw,et al.  Clonogenic cell survival and rejoining of DNA double-strand breaks: comparisons between three cell lines after photon or He ion irradiation. , 1994, International journal of radiation biology.

[31]  H. Dertinger,et al.  The DNA content of some mammalian cells measured by flow cytometry and its influence on radiation sensitivity. , 1990, International journal of radiation biology.

[32]  G. Steel,et al.  Induction and rejoining of DNA double-strand breaks in human cervix carcinoma cell lines of differing radiosensitivity. , 1988, Radiation research.

[33]  K. Prise,et al.  The irradiation of V79 mammalian cells by protons with energies below 2 MeV. Part II. Measurement of oxygen enhancement ratios and DNA damage. , 1990, International journal of radiation biology.

[34]  P. O'Neill,et al.  Induction and rejoining of DNA double-strand breaks in V79-4 mammalian cells following gamma- and alpha-irradiation. , 1993, International journal of radiation biology.

[35]  K M Prise,et al.  A review of dsb induction data for varying quality radiations. , 1998, International journal of radiation biology.

[36]  Maria Antonella Tabocchini,et al.  Proton irradiation facility for radiobiological studies at a 7 MV Van de Graaff accelerator , 1987 .