Mariagabriella Pugliese

Bio: Mariagabriella Pugliese is an academic researcher from University of Naples Federico II. The author has contributed to research in topics: Radon & Electromagnetic shielding. The author has an hindex of 21, co-authored 126 publications receiving 1588 citations. Previous affiliations of Mariagabriella Pugliese include Istituto Nazionale di Fisica Nucleare.

Inactivation of human normal and tumour cells irradiated with low energy protons.

Abstract: 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/ μ m. 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 resista...

Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged particles.

Abstract: We have recently reported the kinetics of chromosome rejoining and exchange formation in human lymphocytes exposed to gamma rays using the techniques of fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC). In this paper, we have extended previous measurements to cells exposed to charged particles. Our goal was to determine differences in chromatin break rejoining and misrejoining after exposure to low- and high-linear energy transfer (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for various times after exposure. Little difference was observed in the yield of early prematurely condensed chromosome breaks for the different ions. The kinetics of break rejoining was exponential for all ions and had similar time constants, but the residual level of unrejoined breaks after prolonged incubation was higher for high-LET radiation. The kinetics of exchange formation was also similar for the different ions, but the yield of chromosome interchanges measured soon after exposure was higher for high-LET particles, suggesting that a higher fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of formation of complete exchanges was slightly lower for densely ionizing radiation. The ratios between the yields of different types of aberrations observed at 10 h postirradiation in prematurely condensed chromosome preparations were dependent on LET. We found significant differences between the yields of aberrations measured in interphase (after repair) and metaphase for densely ionizing radiation. This difference might be caused by prolonged mitotic delay and/or interphase death. Overall, the results point out significant differences between low- and high-LET radiation for the formation of chromosome aberrations.

Cytogenetic Effects of High-Energy Iron Ions: Dependence on Shielding Thickness and Material

Abstract: Durante, M., George, K., Gialanella, G., Grossi, G., La Tessa, C., Manti, L., Miller, J., Pugliese, M., Scampoli, P. and Cucinotta, F. A. Cytogenetic Effects of High-Energy Iron Ions: Dependence on Shielding Thickness and Material. Radiat. Res. 164, 571–576 (2005). We report results for chromosomal aberrations in human peripheral blood lymphocytes after they were exposed to high-energy iron ions with or without shielding at the HIMAC, AGS and NSRL accelerators. Isolated lymphocytes were exposed to iron ions with energies between 200 and 5000 MeV/ nucleon in the 0.1–1-Gy dose range. Shielding materials consisted of polyethylene, lucite (PMMA), carbon, aluminum and lead, with mass thickness ranging from 2 to 30 g/cm2. After exposure, lymphocytes were stimulated to grow in vitro, and chromosomes were prematurely condensed using a phosphatase inhibitor (calyculin A). Aberrations were scored using FISH painting. The yield of total interchromosomal exchanges (including dicentrics, translocations and co...

Effectiveness of monoenergetic and spread-out Bragg peak carbon ions for inactivation of various normal and tumour human cell lines

Abstract: Human cell line/Carbon-ion beams/Cell inactivation/Relative Biological Effectiveness (RBE)/Linear Energy Transfer (LET) This work aimed at measuring cell-killing effectiveness of monoenergetic and Spread-Out Bragg Peak ( SOBP) carbon-ion beams in normal and tumour cells with different radiation sensitivity Clonogenic survival was assayed in normal and tumour human cell lines exhibiting different radiosensitivity to X- or γ-rays following exposure to monoenergetic carbon-ion beams (incident LET 13–303 keV/μm) and at various positions along the ionization curve of a therapeutic carbon-ion beam, corresponding to three doseaveraged LET (LETd) values (40, 50 and 75 keV/μm) Chinese hamster V79 cells were also used Carbon-ion effectiveness for cell inactivation generally increased with LET for monoenergetic beams, with the largest gain in cell-killing obtained in the cells most radioresistant to X- or γ-rays Such an increased effectiveness in cells less responsive to low LET radiation was found also for SOBP irradiation, but the latter was less effective compared with monoenergetic ion beams of the same LET Our data show the superior effectiveness for cell-killing exhibited by carbon-ion beams compared to lower LET radiation, particularly in tum our cells radioresistant to X- or γ-rays, hence the advantage of using such beams in radiotherapy The observed lower effectiveness of SOBP irradiation compared to monoenergetic carbon beam irradiation argues against the radiobiological equivalence between dose-averaged LET in a point in the SOBP and the corresponding monoenergetic beams

Accelerator-based tests of radiation shielding properties of materials used in human space infrastructures.

Abstract: Shielding is the only practical countermeasure for the exposure to cosmic radiation during space travel It is well known that light, hydrogenated materials, such as water and polyethylene, provide the best shielding against space radiation Kevlar and Nextel are two materials of great interest for spacecraft shielding because of their known ability to protect human space infrastructures from meteoroids and debris We measured the response to simulated heavy-ion cosmic radiation of these shielding materials and compared it to polyethylene, Lucite (PMMA), and aluminum As proxy to galactic nuclei we used 1 GeV n iron or titanium ions Both physics and biology tests were performed The results show that Kevlar, which is rich in carbon atoms (about 50% in number), is an excellent space radiation shielding material Physics tests show that its effectiveness is close (80-90%) to that of polyethylene, and biology data suggest that it can reduce the chromosomal damage more efficiently than PMMA Nextel is less efficient as a radiation shield, and the expected reduction on dose is roughly half that provided by the same mass of polyethylene Both Kevlar and Nextel are more effective than aluminum in the attenuation of heavy-ion dose

Relative biological effectiveness (RBE) values for proton beam therapy.

Abstract: Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs. As substantial clinical experience and additional experimental determinations of RBE have accumulated and the number of proton radiation therapy centers is projected to increase, it is appropriate to reassess the rationale for the continued use of a generic RBE and for that RBE to be 1.0–1.1. Methods and Materials: Results of experimental determinations of RBE of in vitro and in vivo systems are examined, and then several of the considerations critical to a decision to move from a generic to tissue-, dose/fraction-, and LET-specific RBE values are assessed. The impact of an error in the value assigned to RBE on normal tissue complication probability (NTCP) is discussed. The incidence of major morbidity in proton-treated patients at Massachusetts General Hospital (MGH) for malignant tumors of the skull base and of the prostate is reviewed. This is followed by an analysis of the magnitude of the experimental effort to exclude an error in RBE of ≥10% using in vivo systems. Results: The published RBE values, using colony formation as the measure of cell survival, from in vitro studies indicate a substantial spread between the diverse cell lines. The average value at mid SOBP (Spread Out Bragg Peak) over all dose levels is ≈1.2, ranging from 0.9 to 2.1. The average RBE value at mid SOBP in vivo is ≈1.1, ranging from 0.7 to 1.6. Overall, both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. There is agreement that there is a measurable increase in RBE over the terminal few millimeters of the SOBP, which results in an extension of the bioeffective range of the beam in the range of 1–2 mm. There is no published report to indicate that the RBE of 1.1 is low. However, a substantial proportion of patients treated at ≈2 cobalt Gray equivalent (CGE)/fraction 5 or more years ago were treated by a combination of both proton and photon beams. Were the RBE to be erroneously underestimated by ≈10%, the increase in complication frequency would be quite serious were the complication incidence for the reference treatment ≥3% and the slope of the dose response curves steep, e.g., a γ50 ≈ 4. To exclude ≥1.2 as the correct RBE for a specific condition or tissue at the 95% confidence limit would require relatively large and multiple assays. Conclusions: At present, there is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc. The experimental in vivo and clinical data indicate that continued employment of a generic RBE value and for that value to be 1.1 is reasonable. However, there is a local “hot region” over the terminal few millimeters of the SOBP and an extension of the biologically effective range. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in laboratory animal systems, especially as a function of dose/fraction in the range of 1–4 Gy.

Role of cell cycle in mediating sensitivity to radiotherapy.

Abstract: Multiple pathways are involved in maintaining the genetic integrity of a cell after its exposure to ionizing radiation. Although repair mechanisms such as homologous recombination and nonhomologous end-joining are important mammalian responses to double-strand DNA damage, cell cycle regulation is perhaps the most important determinant of ionizing radiation sensitivity. A common cellular response to DNA-damaging agents is the activation of cell cycle checkpoints. The DNA damage induced by ionizing radiation initiates signals that can ultimately activate either temporary checkpoints that permit time for genetic repair or irreversible growth arrest that results in cell death (necrosis or apoptosis). Such checkpoint activation constitutes an integrated response that involves sensor (RAD, BRCA, NBS1), transducer (ATM, CHK), and effector (p53, p21, CDK) genes. One of the key proteins in the checkpoint pathways is the tumor suppressor gene p53, which coordinates DNA repair with cell cycle progression and apoptosis. Specifically, in addition to other mediators of the checkpoint response (CHK kinases, p21), p53 mediates the two major DNA damage-dependent cellular checkpoints, one at the G(1)-S transition and the other at the G(2)-M transition, although the influence on the former process is more direct and significant. The cell cycle phase also determines a cell's relative radiosensitivity, with cells being most radiosensitive in the G(2)-M phase, less sensitive in the G(1) phase, and least sensitive during the latter part of the S phase. This understanding has, therefore, led to the realization that one way in which chemotherapy and fractionated radiotherapy may work better is by partial synchronization of cells in the most radiosensitive phase of the cell cycle. We describe how cell cycle and DNA damage checkpoint control relates to exposure to ionizing radiation.

Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer

Abstract: Proton therapy treatments are based on a proton RBE (relative biological effectiveness) relative to high-energy photons of 1.1. The use of this generic, spatially invariant RBE within tumors and normal tissues disregards the evidence that proton RBE varies with linear energy transfer (LET), physiological and biological factors, and clinical endpoint.Based on the available experimental data from published literature, this review analyzes relationships of RBE with dose, biological endpoint and physical properties of proton beams. The review distinguishes between endpoints relevant for tumor control probability and those potentially relevant for normal tissue complication. Numerous endpoints and experiments on sub-cellular damage and repair effects are discussed.Despite the large amount of data, considerable uncertainties in proton RBE values remain. As an average RBE for cell survival in the center of a typical spread-out Bragg peak (SOBP), the data support a value of ~1.15 at 2 Gy/fraction. The proton RBE increases with increasing LETd and thus with depth in an SOBP from ~1.1 in the entrance region, to ~1.15 in the center, ~1.35 at the distal edge and ~1.7 in the distal fall-off (when averaged over all cell lines, which may not be clinically representative). For small modulation widths the values could be increased. Furthermore, there is a trend of an increase in RBE as (α/β)x decreases. In most cases the RBE also increases with decreasing dose, specifically for systems with low (α/β)x. Data on RBE for endpoints other than clonogenic cell survival are too diverse to allow general statements other than that the RBE is, on average, in line with a value of ~1.1.This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties to clinically acceptable levels.

Heavy ion carcinogenesis and human space exploration

Abstract: Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets