J.C. Mateos

Human adipose cells have voltage-dependent potassium currents

The whole-cell patch-clamp method was used to study the membrane electrical properties of human adipocyte cells obtained by differentiating from precursors of human abdominal and mammary tissues. All differentiated cells exhibited outward currents with sigmoidal activation kinetics. The outward currents showed activation thresholds between −20 to −30 mV and slow inactivation. The ionic channels underlying the macroscopic current were highly selective for K+. Their selectivity was for typical K+ channels with relative permeabilities of K+>NH4+>Cs+>Na+. No evidence of any other type of voltage-gated channel was found. The potassium currents (IKV) were blocked reversibly by tetraethylammonium and barium. The IC50 value and Hill coefficient of tetraethylammonium inhibition of IKV were 0.56 mM and 1.17 respectively. These results demonstrate that human adipose cells have voltage-dependent potassium currents.

Topoisomerase activities and levels in irradiated Chinese hamster AA8 cells and in its radiosensitive mutant EM9

PURPOSE To investigate possible variations in topoisomerase (topo) I and II activities and levels after X-ray treatment in the radiation repair proficient AA8 Chinese hamster cell line for comparison with the radiation sensitive mutant EM9. MATERIALS AND METHODS AA8 and EM9 cells were irradiated with 5 Gy of X-rays and the activities of topoisomerases I and II in nuclear extracts were studied. Immunological detection of both topoisomerases was carried out in order to detect any changes in the expression of these enzymes as a consequence of irradiation. RESULTS Topoisomerase activities and levels in irradiated EM9 cells were the same as in control non-irradiated cells. In fact, both topo I and topo II activities clearly increased shortly after irradiation in the parental AA8 cells, with a more rapid increase for topo I than for topo II. In the AA8 cells, an increased level of topo I detectable immunologically was only observed at a later time (1 h) after irradiation, while no similar change was detectable for topo II. CONCLUSIONS While this hypothesis needs further testing, an attractive idea is that DNA topoisomerases might be involved in the cellular response to radiation damage, either through a direct participation in repair mechanisms or indirectly.

3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry

A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.

A comparative study of the potentiating effect of caffeine and poly-D-lysine on chromosome damage induced by X-rays in plant cells.

X-Ray-induced chromosomal aberrations (CA) were potentiated by post-treatments in G2 with either caffeine (caff) or poly-D-lysine (PDL) in root-tip cells of Allium cepa. The enhancement of the yield of CA was concomitant with an increase in the frequency of mitosis. Our results seem to support the idea of a direct relationship between radiation-induced G2 delay and repair of chromosome damage. Here we report on similarities between caffeine and PDL in both decreasing G2 delay and enhancing chromatid aberration yield. The possible molecular mechanism(s) of action responsible for the cytogenetic effects observed are discussed.

Poly-d-lysine in G2 potentiates chromosome damage induced by X-rays and mitomycin C in CHO cells

A number of reports suggest that the role of radiation-induced G2 arrest is to allow repair of potentially lethal damage in the cells before it comes to mitosis. Though the exact nature of the damage undergoing repair during the delayed G2 is not known, the yield of chromosomal aberrations observed in metaphase seems to be a good parameter to predict reproductive death of cells. In a previous paper, we have shown that poly-D-lysine, acting in a fashion reminiscent of that of caffeine in mammalian cells, is able to induce a premature onset of mitosis concomitant with an increase in the frequency of chromosomal aberrations in mutagen-treated plant cells. Cultured CHO cells were pre-exposed to either X-rays or mitomycin C and given different doses of the polycationic compound during G2 in order to analyze any effect on the frequency of chromatid-type aberrations as well as any modification of cell-cycle kinetics. A potentiation of chromosome damage and a premature arrival at mitosis were observed for both mutagens, though the effect was more evident in X-irradiated cells.

SU-E-T-644: QuAArC: A 3D VMAT QA System Based On Radiochromic Film and Monte Carlo Simulation of Log Files

Purpose: VMAT involves two main sources of uncertainty: one related to the dose calculation accuracy, and the other linked to the continuous delivery of a discrete calculation. The purpose of this work is to present QuAArC, an alternative VMAT QA system to control and potentially reduce these uncertainties. Methods: An automated MC simulation of log files, recorded during VMAT treatment plans delivery, was implemented in order to simulate the actual treatment parameters. The linac head models and the phase-space data of each Control Point (CP) were simulated using the EGSnrc/BEAMnrc MC code, and the corresponding dose calculation was carried out by means of BEAMDOSE, a DOSXYZnrc code modification. A cylindrical phantom was specifically designed to host films rolled up at different radial distances from the isocenter, for a 3D and continuous dosimetric verification. It also allows axial and/or coronal films and point measurements with several types of ion chambers at different locations. Specific software was developed in MATLAB in order to process and evaluate the dosimetric measurements, which incorporates the analysis of dose distributions, profiles, dose difference maps, and 2D/3D gamma index. It is also possible to obtain the experimental DVH reconstructed on the patient CT, by an optimization method to find the individual contribution corresponding to each CP on the film, taking into account the total measured dose, and the corresponding CP dose calculated by MC. Results: The QuAArC system showed high reproducibility of measurements, and consistency with the results obtained with the commercial system implemented in the verification of the evaluated treatment plans. Conclusion: A VMAT QA system based on MC simulation and high resolution dosimetry with film has been developed for treatment verification. It shows to be useful for the study of the real VMAT capabilities, and also for linac commissioning and evaluation of other verification devices.

The best prostate plan ever: A quantification of the therapeutic window

Finding out the best treatment plan that could be designed for a specific patient could be a difficult task. Benefits on terms of better tumor coverage have to be balanced against the drawbacks of poorer organ at risk sparing in order to make the decision on the optimum treatment technique. A large variety of photon beam radiotherapy (RT) techniques are currently available. The relative merits of different 34 treatment modalities for a prostate cancer, using the same CT data set and contours, have been analyzed in terms of the area under the Uncomplicated Control Probability curve. IMRT forward techniques have resulted to be the best ranked treatment modalities.