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M A Tabocchini

Publications and source records attributed to M A Tabocchini.

26 records · Page 2Linked to original sources
PubMed1993

Inactivation and mutation induction in V79 cells by low energy protons: re-evaluation of the results at the LNL facility.

During the upgrading of the radiobiological facility at the Laboratori Nazionali di Legnaro (LNL) we found that uncorrected values of the proton energy were used in the past. This circumstance prompted us to perform the re-evaluation of the physical parameters for all the proton beams used in our previous radiobiological investigations (Belli et al. 1987) and, subsequently, the re-evaluation of all our previous dose-response curves for inactivation and mutation induction (Belli et al. 1989, 1991). This re-evaluation leads to significant changes in the dose-response curves and in the RBE-LET relationships only at the two lowest energies (highest LET) used. These two points are not reliable for the identification of a peak in RBE-LET relationship for cell inactivation. In spite of that, the extent of the changes is not such as to modify the general conclusion previously drawn, pointing out that there is a LET range where protons are more effective than alpha-particles.

Animals↗
PubMed1992

Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. II. Mutation induction at the HPRT locus in V79 cells.

Mutation induction at the hprt locus has been studied in V79-4 Chinese hamster cells irradiated with mono-energetic protons and alpha-particles with LET of 20.3 and 23 keV microns-1. The mutation frequency increased linearly with the dose for all the four radiation qualities investigated, so that effectiveness for mutation induction could be expressed by the slope of the relevant curve. This effectiveness did not significantly change with the small change in LET of each kind of particle, while sizeable differences were found between particles. Protons were more effective in mutation induction than alpha-particles with the same LET by a factor of about 2. This finding is similar to, although slightly larger than, the factors 1.5-1.8 found for inactivation of the same cells in the same series of experiments.

Alpha Particles↗
PubMed1992

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.

The results reported form part of a series of experiments to substantiate and extend the findings by Belli et al. (1989) that protons are more biologically effective at cell killing than alpha-particles of the same LET. The irradiations were carried out using the Variable Energy Cyclotron (VEC) at the Harwell Laboratories. V79-4 Chinese hamster cells were exposed to alpha-particles and protons with LETs of 20 and 23 keV microns-1 in the dose range 40-150 Gy. X-rays were also used for comparison. Two methods were used for measurement of initial DNA double-strand breaks: sedimentation and DNA precipitation assays. The dose-response relationships were found to be well fitted by straight lines in all cases. With the sedimentation assay a slightly lower yield of dsb was found from protons than from alpha-particles of the same LET. The yield from X-rays was not significantly different from either. The precipitation assay showed similar yields of DNA damage from both particle types but significantly higher yields from X-rays. This may reflect a difference in the type of lesions scored by the two methods. Since the initial amount of dsb does not account for the observed differences in cellular response to radiations of different qualities, it is likely that these are related to the nature of the dsb (affecting reparability) or to the occurrence of other types of molecular damage.

Alpha Particles↗
PubMed1991

Mutation induction and RBE-LET relationship of low-energy protons in V79 cells.

The mutation induction at the HGPRT locus has been studied in V79-753B Chinese hamster cells irradiated with proton beams with energies of 3.36, 1.70 and 1.16 MeV, corresponding to average LET values of 10.6, 17.8 and 23.9 keV/microns, respectively. The mutation curve obtained with 200 kV X-rays was used for comparison. The mutation frequency induced by all the proton beams is considerably higher than that induced at the same dose by X-rays and it is linearly related to the dose. Moreover, the proton effectiveness increases with the LET. The RBEs (evaluated as the initial slope ratios) are 5.0 +/- 0.8, 5.4 +/- 0.8 and 7.7 +/- 1.2 for protons with average LETs of 10.6, 17.8 and 23.9 keV/microns, respectively. These values are higher than those reported in the literature for other ions of comparable LET. This finding parallels what we have already found for cell inactivation (for which RBEs of 3.0, 4.6 and 7.3 were obtained at the same LETs), and indicates that for mutation induction, also, the RBE-LET relationship may depend on the type of radiation.

Animals↗
PubMed1991

Relationships between cell killing, mutation induction and DNA damage in X-irradiated V79 cells: the influence of oxygen and DMSO.

The relationships between cell killing, mutation induction and DNA double (dsb) and single (ssb) strand breaks have been studied in V79 cells irradiated with X-rays under oxic and anoxic conditions in the presence and in the absence of dimethylsulphoxide (DMSO). Curvilinear relationships were found between all pairs of endpoints, except for dsb versus ssb. Statistical analysis of experimental data has shown that in the absence of DMSO there is evidence of good correlations between cell killing, mutation induction and dsb in oxic and anoxic conditions. However, when DMSO was present, no significant correlation was found. In the presence of oxygen DMSO always exerts a protective effect while in anoxia it is generally much less protective and induces a strong sensitization with respect to mutation induction. Possibly DMSO acts not only as a radical scavenger but also as an agent inducing chromatin relaxation and/or under anoxia, forming highly mutagenic short-term radicals. The present data suggest that lethal and mutational events are at least partially independent and not proportional to the initial number of DNA breaks. This may imply that either other kinds of lesions are involved in cell lethality and mutability, or dose-dependent repair mechanisms of dsb have to be considered.

Animals↗
PubMed1989

RBE-LET relationship for the survival of V79 cells irradiated with low energy protons.

The survival of V79 Chinese hamster cells irradiated with proton beams with energies of 0.73, 0.84, 1.16, 1.70 and 3.36 MeV, corresponding to LET values, evaluated at the cell midplane, of 34.5, 30.4, 23.9, 17.8 and 10.6 keV/micron respectively, have been studied in the dose range 0.5-6.0 Gy. As a reference, the survival curve obtained with 200 kV X-rays was used. The initial shoulder, typical of survival curves obtained with sparsely ionizing radiation, decreases as the LET increases and completely disappears at 23.9 keV/micron. This value corresponds to the maximum of the RBE, expressed as the initial slope ratio. In the energy range we have considered, the RBEs for protons are higher than those reported for other ions of comparable LET and the RBE-LET relationship results shifted to lower LET values. Our data seem to indicate that the RBE-LET curve depends on the type of radiation and this could imply that LET is not a good reference for the dose-effectiveness relationship.

Animals↗
PubMed1989

Radiation damage and chromatin structure.

The recent advances made in the knowledge of chromatin structure have important implications in molecular and cellular radiobiology. There are now many lines of evidence that the chromatin organization can affect the production, the distribution and the repair of radiation-induced damage in DNA. Experiments with polynucleosomes show that DNA double strand breaks (dsb) are not randomly distributed along the DNA molecule. Rather, they are preferentially localized in linker regions, while core regions are more resistant. Isolated DNA is about 4-fold more susceptible to dsb than DNA irradiated as a part of polynucleosomes. This differential radiosensitivity is apparently due to the close association of DNA with proteins. The analysis of DNA single strand breaks production and repair in a human erythroleukemic cell line that can be induced to differentiate in vitro, showed that the repair kinetics in differentiated cells appears significantly slower than in undifferentiated ones. This can be interpreted as a decrease in the genome accessibility to repair enzymes due to the presence of more structured regions in chromatin after differentiation. It appears that a high degree of genome compactness could imply, on one hand, a high DNA radioresistance and, on the other hand, a slow DNA repair so that the identification of chromatin domains which are critical, from the structural point of view, in determining cellular effects such as cell killing and mutation, should take into account a sort of balance between the amount of damage and the extent of repair.

Animals↗