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Purpose: To examine the low-dose sensitivity of V79 cells under exposure to γ-rays and [sup 4]He ions of different energies. Materials and methods: Cell survival and cytogenetic analysis using the Giemsa technique were studied following irradiation to doses of 0-3 Gy at the INFN-LNL facilities. Results: Low-dose hyper-radiosensitivity (HRS) of V79 was demonstrated after irradiation with γ-rays and α-particles of various linear energy transfers (LET) (58.9, 79.3 and 101.7 keV μm[sup -1]). Cytogenetic analysis showed an LET dependence of aberrations at a dose of 1Gy; the frequency of chromatid fragments appeared to vary with the number of α-particles traversing the cell nucleus. The results of both studies fit together to give a better understanding of so-called 'induced radioresistance' phenomenon. Conclusions: The mechanism of induced cellular radioresistance appears to be initiated after a certain amount of energy is deposited in the cell nucleus. This amount depends on both radiation quality and the number of particles traversing the cell. [ABSTRACT FROM AUTHOR]

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 2h 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. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the cell inactivation frequencies induced by low energy protons in human cells with different sensitivity to photon radiation. Materials and methods: Four human cell lines with various sensitivities to photon irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours of the tongue and larynx, respectively, and the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were irradiated with γ-rays and proton beams with linear energy transfer (LET) from 7 to 33keV/μm. Clonogenic survival was assessed. Results: Survival curves are reported for each cell line following irradiation with γ-rays and with various proton LETs. The surviving fraction after 2 Gy of γ-rays was 0.72 for SQ20B cells, and 0.28–0.35 for the other cell lines. The maximum LET proton effectiveness was generally greater than that of γ-rays. In particular there was a marked increase in beam effectiveness with increasing LET for the most resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with γ-radiation down to 0.37 with 30keV/μm protons. The relative biological effectiveness (RBE(2Gy γ)) with the 30 keV/μm beam, evaluated as the ratio of 2Gy to the proton dose producing the same inactivation level as that given by 2 Gy of γ-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively. Conclusions: RBE for inactivation with high-LET protons increased with the cellular radioresistance to γ-rays. The cell line with the greatest resistance to γ-rays was the most responsive to the highest LET proton beam. A similar trend has also been found in studies reported in the literature with He, C, N ions with LET in the range 20–125keV/μm on human tumour cell lines. [ABSTRACT FROM AUTHOR]

Purpose: To study the relative biological effectiveness-linear energy transfer (RBE-LET) relationship for micronuclei (MN) and cell inactivation, in Chinese hamster cells irradiated with low-energy protons (0.88 and 5.04 MeV, at the cell entrance surface). Chromosome loss was also investigated by means of antikinetochore CREST staining. Materials and methods: Cl-1 cells were exposed to different doses of X-rays, gamma-rays, 7.7 keV/mum and 27.6 keV/mum protons. The induction of MN, the distribution of MN per cell and the frequency of CREST-positive MN were evaluated in cytokinesis-blocked binucleated cells (BN cells) in the dose range 0.125-3 Gy. In parallel, cell survival experiments were carried out in samples irradiated with 0.5 to 4 Gy. Results: MN yield and the frequency of BN cells carrying multiple MN ( 2) were significantly higher after exposure to 27.6 keV/mum protons, compared with the other radiation types. In contrast, MN induction and MN distribution per BN cell were similar among 7.7 keV/mum protons, X- and gamma-rays up to 1 Gy. Cell survival experiments gave RBE values very close to those obtained with the MN assay. Both X-rays and 27.6keV/mum protons yielded a significant proportion of CREST-positive MN at the highest doses investigated (0.75-3Gy). Conclusions: Good correlations between MN induction and cell inactivation were observed for both low- and high-LET radiation, indicating that the MN assay can be a useful tool to predict cell sensitivity to densely ionizing radiation with implications for tumour therapy with protons. [ABSTRACT FROM AUTHOR]

Purpose: To determine the yield of mitotic catastrophe induced after low energy proton irradiation and to compare this yield with that induced by X-rays. Materials: Asynchronous Chinese hamster V79 cells were irradiated with 0.5, 1, 2, 5 and 10Gy proton beams and X-rays. Proton LET of 7.7, 11.0 and 30.5keV mu m1, corresponding to energies of 5.01, 3.20 and 0.76MeV respectively, evaluated at the cell mid-plane, were used for experiments. The occurrence and yield of mitotic catastrophe was measured as the percentage of cells exhibiting fragmented nuclei. Results: Proton irradiation led to an enhanced induction of mitotic catastrophe in V79 cells. The onset of nuclear fragmentation, a hallmark of mitotic catastrophe, occurred much earlier after cell exposure to proton particles than to X-ray irradiation. Conclusions: Mitotic catastrophe is persistent in the subsequent cell generations after proton and X irradiation of V79 cells; but protons are more effective than X-rays for the induction of this phenomenon. These results are discussed in terms of their importance in space exposures and possible acquisition of genomic instability by the progeny of irradiated cells. [ABSTRACT FROM AUTHOR]

Purpose: RBE-LET relationships for cell inactivation and hprt mutation in V79 cells have been studied with mono-energetic low-energy proton beams at the radiobiological facility of the INFN-Laboratori Nazionali di Legnaro (LNL), Padova, Italy. Materials and methods : V79 cells were irradiated in mono-layer on mylar coated stainless steel petri dishes, in air. Inactivation data were obtained at 7.7, 34.6 and 37.8 keV/ mu m and hprt mutation was studied at 7.7 and 37.8 keV/ mu m. Additional data were also collected for both the end points with the proton LET already considered in our previous publications, namely 11.0, 20.0 and 30.5keV/ mu m. Results : A maximum in the RBE-LET relationship for cell inactivation was found at around 31keV/ mu m, while the RBE for mutation induction increased continuously with LET. Conclusions : The proton RBE-LET relationship for cell inactivation is shifted to lower LET values compared with that for heavier ions. For mutation induction, protons of LET equal to 7.7 keV/ mu m gave an RBE value comparable with that obtained by helium ions of about 20 keV/ mu m. Mutagenicity and lethality caused by protons at low doses in the LET range 7.7-31keV/ mu m were proportional, while the data at 37.8keV/ mu m suggest that this may not hold at higher LET values. [ABSTRACT FROM AUTHOR]

Purpose: To determine the RBE-LET relationship for C3H10T1/2 cell inactivation by protons in the LET range 11-33 keV/ mu m and to compare inactivation frequencies induced in C3H10T1/2 cells by protons and deuterons at two matching LET values in the range 11-20 keV/ mu m. Materials and methods: C3H10T1/2 cells were irradiated with protons and deuterons at the radiobiological facility set up at the 7 MV Van de Graaff accelerator at the LNL, Legnaro, Padova. Gamma rays from 60Co were used as reference radiation. Results: Proton RBE values ( alpha / alpha c ) for inactivation of C3H10T1/2 cells are constant around a value of 2 between 11 and 20 keV/ mu m and then rise sharply to reach a value of 4.2 1.0 at 33 keV/ mu m. Deuteron RBE values are 1.7 0.4 and 2.2 0.6 at LET values of 13 and 18 keV/ mu m respectively. Conclusions: Proton RBE values with C3H10T1/2 cells are significantly larger than unity at LET values as low as 11 keV/ mu m. No difference in effectiveness for inactivation of C3H10T1/2 has been found between protons and deuterons at two LET values in the range 10-20 keV/ mu m. [ABSTRACT FROM AUTHOR]

Purpose: Biological effects produced by low doses of ionizing radiations, though relevant for the risk assessment, have not been fully elucidated. The aim of the present work was to evaluate cytogenetic endpoints, as telomere dysfunctions and chromosome instability in the low-dose range as a function of radiation quality. In particular, we analyzed whether the telomere length was modulated, as well as the involvement of telomeres in chromosomal alterations at anaphase, and the yield of stable simple and complex chromosome aberrations., Materials and Methods: AG01522 human primary fibroblasts were irradiated with 0.1-1 Gy of X-rays, protons (28.5 keV/μm), and 4He(2+) ions (62 keV/μm). Frequency of chromosome bridges carrying or not telomeric signals and telomere length were measured in irradiated samples up to 72 h. Moreover, chromosome instability was measured using multicolor fluorescence in situ hybridization (mFISH)., Results: The results evidenced a linear energy transfer (LET)- and dose-dependent response in the frequency of anaphase bridges induction and in their persistence as a function of time. However, neither variation in telomere length and telomere loss, nor in the proportion of bridges bearing telomeric signals, was detected, thus indicating a minor role of telomeres in the generation of the radiation-induced chromosome bridges. Chromosome instability followed a linear-dependence with dose and LET, showing a far higher extent of complex translocations in helium-ion-irradiated cells than in proton- or X-ray-irradiated samples., Conclusions: Altogether, the results indicated the lack of telomere involvement in cytogenetic effects induced by low-dose ionizing radiation. On the contrary, chromosome aberration yield and spectrum were LET- and dose-dependent.

Purpose: To examine the low-dose sensitivity of V79 cells under exposure to gamma-rays and 4He ions of different energies., Materials and Methods: Cell survival and cytogenetic analysis using the Giemsa technique were studied following irradiation to doses of 0-3 Gy at the INFN-LNL facilities., Results: Low-dose hyper-radiosensitivity (HRS) of V79 was demonstrated after irradiation with gamma-rays and alpha-particles of various linear energy transfers (LET) (58.9, 79.3 and 101.7 keV microm(-1)). Cytogenetic analysis showed an LET dependence of aberrations at a dose of 1Gy; the frequency of chromatid fragments appeared to vary with the number of alpha-particles traversing the cell nucleus. The results of both studies fit together to give a better understanding of so-called 'induced radioresistance' phenomenon., Conclusions: The mechanism of induced cellular radioresistance appears to be initiated after a certain amount of energy is deposited in the cell nucleus. This amount depends on both radiation quality and the number of particles traversing the cell.