Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay.

Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140µM curcumin and 2.2 to 220µM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity testing, which simulates conditions similar to those of the highly radiosensitive lymphocytes of AT patients. The results demonstrate for the first time the cell-cycle-dependent action of these polyphenols. When non-cycling cells are irradiated, the radioprotective properties of curcumin and trans-resveratrol are more prominent. However, when cycling cells are irradiated during G2-phase, the radiosensitizing features of these compounds are more pronounced. This observation offers a new biological basis for the mechanisms underlying the action of these polyphenols in cancer radiotherapy.

Assessment in vitro of cytogenetic and genotoxic effects of propolis on human lymphocytes.

We evaluated the genetic damage by ethanolic extract of propolis (EEP) induced to human lymphocytes which were exposed to increasing concentrations (0-2000µgml(-1)). The results indicated that EEP reduced significantly the mitotic index (MI) and proliferation index (PI) when high concentrations of EEP were used. Sister chromatid exchange (SCE) rates indicated that EEP could have genotoxic effects at high concentrations. Exposure of the cells to the amount of ethanol used as solvent did not alter either the MI and cell proliferation kinetics (CPK), or the rate of SCE. The results showed: (a) statistical increase in the percentage the cells with CAs and in the frequency of SCE at the highest concentrations, (b) a decrease in MI and in the CPK values was observed, (c) no effect was noticed in negative controls. In conclusion, it can be assumed that high concentrations of EEP have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes.

Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes.

Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 µg mL(-1) and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 µg mL(-1) of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation.

Biological and physical methods for risk estimation in interventional radiology: a detrimental effect approach.

Interventional radiologists and staff members are frequently exposed to the effects of direct and scattered radiation, which undergo in deterministic effects (radiodermitis, aged skin, cataracts, telangiectasia in nasal region, vasocellular epitelioms, hands depilation) and/or stochastic ones (cancer incidence). A methodology has been proposed for estimating the radiation risk or detriment from a group of six exposed interventional radiologists of the Hospital Universitario La Fe (Valencia, Spain), which had developed general exposition symptoms attributable to deterministic effects of ionizing radiation. Equivalent doses have been periodically registered using termoluminiscence dosimeters (TLD's) and wrist dosimeters, H(p)(10) and H(p)(0.07), respectively, and estimated through the observation of translocations in lymphocytes of peripheral blood (biological methods), by extrapolating the yield of translocations to their respective dose-effect curves. The software RADRISK has been applied for estimating radiation risks in these occupational radiation exposures. The minimum and maximum average excess ratio for skin cancer has been, using wrist physical doses, of [1.03 × 10(-3), 5.06 × 10(-2)], concluding that there is not an increased risk of skin cancer incidence. The minimum and maximum average excess ratio for leukemia has been, using TLD physical doses, of [7.84 × 10(-2), 3.36 × 10(-1)], and using biological doses, of [1.40 × 10(-1), 1.51], which is considerably higher than incidence rates, showing an excess radio-induced risk of leukemia in the group under study. Finally, the maximum radiological detriment in the group, evaluated as the total number of radio-induced cancers using physical dosimetry, has been of 2.18 per 1000 person-year (skin and leukemia), and using biological dosimetry of 9.20 per 1000 PY (leukemia). As a conclusion, this study has provided an assessment of the non-deterministic effects (rate of radio-induced cancer incidence) attributable to the group under study due to their professional activity.

Radiation effects analysis in a group of interventional radiologists using biological and physical dosimetry methods.

Interventional radiologists and staff members are frequently exposed to protracted and fractionated low doses of ionizing radiation, which extend during all their professional activities. These exposures can derive, due to the effects of direct and scattered radiation, in deterministic effects (radiodermitis, aged skin, cataracts, telangiectasia in nasal region, vasocellular epitelioms, hands depilation) and/or stochastic ones (cancer incidence). A methodology has been proposed for estimating the radiation risk or detriment from a group of six exposed interventional radiologists of the Hospital Universitario La Fe (Valencia, Spain), which had developed general exposition symptoms attributable to deterministic effects of ionizing radiation. Equivalent doses have been periodically registered using TLD's and wrist dosimeters, H(p)(10) and H(p)(0.07), respectively, and estimated through the observation of translocations in lymphocytes of peripheral blood (biological methods), by extrapolating the yield of translocations to their respective dose-effect curves. The software RADRISK has been applied for estimating radiation risks in these occupational radiation exposures. This software is based on transport models from epidemiological studies of population exposed to external sources of ionizing radiation, such as Hiroshima and Nagasaki atomic bomb survivors [UNSCEAR, Sources and effects of ionizing radiation: 2006 report to the general assembly, with scientific annexes. New York: United Nations; 2006]. The minimum and maximum average excess ratio for skin cancer has been, using wrist physical doses, of [1.03x10(-3), 5.06x10(-2)], concluding that there is not an increased risk of skin cancer incidence. The minimum and maximum average excess ratio for leukemia has been, using TLD physical doses, of [7.84x10(-2), 3.36x10(-1)], and using biological doses, of [1.40x10(-1), 1.51], which is considerably higher than incidence rates, showing an excess radio-induced risk of leukemia in the group under study. Finally, the maximum radiological detriment in the group, evaluated as the total number of radio-induced cancers using physical dosimetry, has been of 2.18/1000 person-year (skin and leukemia), and using biological dosimetry of 9.20/1000 PY (leukemia). As a conclusion, this study has provided an assessment of the non-deterministic effects (rate of radio-induced cancer incidence) attributable to the group under study due to their professional activity.

Unexplained overexposures on physical dosimetry reported by biological dosimetry.

The Medical Service of the Radiation Protection Service from the University Hospital La Fe (Valencia, Spain), carries out medical examinations of the workers occupationally exposed to ionising radiation. The Biological Dosimetry Laboratory is developing its activity since 2001. Up to now, the activities have been focused in performing biological dosimetry studies of Interventionists workers from La Fe Hospital. Recently, the Laboratory has been authorized by the Health Authority in the Valencian Community. Unexplained overexposures of workers and patients are also studied. Workers suspected of being overexposed to ionising radiation were referred for investigation by cytogenetic analysis. Two of these were from Hospitals of the Valencian Community and one belonged to an uranium mine from Portugal. Hospital workers had a physical dose by thermoluminiscence dosimeters (TLD) that exceeded the established limit. The worker of the uranium mine received a dose from a lost source of Cesium 137 with an activity of 170 mCi. All three cases showed normal values after the hematological analysis. Finally, the aim of this study consist to determine whether the dose showed by the dosimeter is reliable or not. In the case of workers that wore dosimeter, it is concluded that the doses measured by dosimeter are not corresponding to real doses. Hospital worker with a physical dose of 2.6 Sv and 0.269 Sv had an estimated absorbed dose by biological dosimetry of 0.076 Gy (0-0.165 Gy) and 0 Gy (0-0.089 Gy), respectively. In case of the mine worker an estimated absorbed dose of 0.073 Gy (0-0.159 Gy) was obtained by biological dosimetry. In all cases we used the odds ratio to present the results due to a very low frequency of observed aberrations [1].

Analysis of the radiological detriment for premenopausal women in a breast early detection program during 2008.

The Valencian Breast Cancer Early Detection Program (VBCEDP) started in the Valencian Community (Spain) in 1992. Up to now, 24 mammographic units have been installed all over the region. Mammography is used to aid in the diagnosis of breast cancer diseases in women. There is a health risk in the studied women due to ionising radiation that has to be estimated and controlled. A methodology to calculate approximately the radiological detriment in the VBCEDP has been developed based on Monte Carlo techniques. It has been used, as qualitative parameter, the average mean glandular dose from representative sample populations undergoing screening mammography (digital or screenfilm) from each of the twenty-four units in operation. The American College of Radiology Imaging Network reached to conclusion that digital mammography performed significantly better than film for pre and perimenopausal women younger than 50. Women who are undergoing the program are between 45 and 69. This fact allows us to study premenopausic women. Our group uses the software SCREENRISK to estimate induction and mortality rates in order to corroborate American conclusions in an European region. The obtained results confirm the American results about the application of digital mammography in pre and perimenopausal women younger than 50 years.

Analysis of digital image quality indexes for CIRS SP01 and CDMAM 3.4 mammographic phantoms.

Mammographic phantom images are usually used to study the quality of images obtained by determined mammographic equipment. The digital image treatment techniques allow carrying out an automatic analysis of the phantom image. Nowadays, the digital radiographic equipments are replacing the traditional film-screen equipments and it is necessary to update the parameters to guarantee the quality of the process. In this work we apply some techniques of digital image processing to compute a specific image quality indexes for mammographic phantoms, namely CIRS SP01 and CDMAM 3.4. to study the evolution of this parameter with different varying conditions of the mammographic equipment. The indexes are calculated from a scoring system based on a designed algorithm which analyses the phantom image by means of an automatic detection of the test objects in each phantom.

Analysis of CR dose reduction in pediatric patients, based on computer-simulated noise addition.

This paper validates a technique to add statistical noise to a Computed Radiography (CR) in order to simulate accurately how the same image would appear if taken at a reduced tube current. To that, a noise addition software has been developed to create lower dose CR using existing pediatric radiographies based on the selection of lower X-ray tube current. The effect of different milliAmpere-seconds (mAs) setting on image quality has been evaluated using the CDMAM 3.4 phantom and the obtained results show good agreements between the simulated and real images in terms of noise measurement. The new CR images allow medical researchers to study how lower dose affects the patient diagnosis.

Study of digital mammographic equipments by phantom image quality.

Nowadays, the digital radiographic equipments are replacing the traditional film-screen equipments and it is necessary to update the parameters to guarantee the quality of the process. Contrast-detail phantoms are applied to digital radiography to study the threshold contrast-detail sensitivity at operation conditions of the equipment. The phantom that is studied in this work is CDMAM 3.4. One of the most extended indexes to measure the image quality in an objective way is the image quality figure (IQF). The aim of this work is to study the image quality of different images contrast-detail phantom CDMAM 3.4, carrying out the automatic detection of the contrast-detail combination and to establish a parameter which characterize in an objective way the mammographic image quality. This is useful to compare images obtained at different digital mammographic equipments to study the functioning of the equipments that facilitates the evaluation of image contrast and detail resolution.

Evaluation of DR and CR digital mammography systems based on phantom and breast dosimetry.

Digital mammography has been progressively introduced in screening centers, since recent evolution of CR and DR detectors. However, it is questionable which exposure conditions would be more suitable when these techniques are applied, in order to reduce the glandular breast doses, as they are related with induced carcinogenesis. Several exposures have been performed in CR and DR mammography units for comparing absorbed doses during quality control assessments and during screening, diagnosis and treatment. In the first case, the CIRS11A mammographic phantom has been used with standard exposure conditions (28 kV, AEC mode with blackening +0, 50:50 glandularity and 4.5 compressed breast thickness) in order to obtain reference values for the standard breast. After that, a sample population of 100 women per mammography unit has been registered for performing a dosimetry study during clinical conditions, using the SCREENDOSE software developed by the authors. Results show that there are significative differences among the mammography units, proving that this methodology could be used for obtaining an objective criterion during the selection of a mammography unit, related with a minimum image quality level for a given clinical use (screening, diagnosis or treatment).

Analysis of shielding materials in a Compton spectrometer applied to x-ray tube quality control using Monte Carlo simulation.

A realistic characterisation of the primary beam is very important for the quality control of X-ray tubes. The most accurate technique to assess the actual photon spectrum is X-ray spectrometry. Some difficulties arising in the spectrum determination can be avoided using a Compton spectrometer. Simulation models are useful tools to know the effect of some operational parameters, such as collimation of primary beam, relative position of focus and detector, and the influence of shielding materials. A simulation model has been developed using the MCNP code, based on the Monte Carlo method, in order to reproduce a commercial Compton spectrometer. In this work, the model developed is applied to analyse the influence on measurements of shielding materials present in the spectrometer.

Assessment by cytogenetic analysis of the radioprotection properties of propolis extract.

Propolis obtained from honeybee hives has been used in folk medicine as an anti-inflammatory, anti-carcinogenic or immunomodulatory agent. In animal studies, the radioprotector effect of propolis has been attributed to its free-radical scavenging properties. The present study was carried out to show the protective properties of propolis extract against DNA damage induced by gamma irradiation. The evaluation of the radioprotective effect of propolis has been carried out by the analysis of chromosome aberration induction after several doses of gamma rays. The results of an analysis in the presence of ethanol extract of propolis (EEP) were compared with the dose-effect calibration curve for gamma-rays by analysis of chromosome aberrations without propolis, a decrease in the radiation-induced chromosome aberrations has been observed to be higher than 50% for all the doses.

Biological dosimetry in a group of radiologists by the analysis of dicentrics and translocations.

The results of a cytogenetic study carried out in a group of nine radiologists are presented. Chromosome aberrations were detected by fluorescence plus Giemsa staining and fluorescence in situ hybridization. Dose estimates were obtained by extrapolating the yield of dicentrics and translocations to their respective dose-effect curves. In seven individuals, the 95% confidence limits of the doses estimated by dicentrics did not include 0 Gy. The 99 dicentrics observed in 17,626 cells gave a collective estimated dose of 115 mGy (95% confidence limits 73-171). For translocations, five individuals had estimated doses that were clearly higher than the total accumulated recorded dose. The 82 total apparently simple translocations observed in 9722 cells gave a collective estimated dose of 275 mGy (132-496). The mean genomic frequencies (x100 +/- SE) of complete and total apparently simple translocations observed in the group of radiologists (1.91 +/- 0.30 and 2.67 +/- 0.34, respectively) were significantly higher than those observed in a matched control group (0.53 +/- 0.10 and 0.87 +/- 0.13, P < 0.01 in both cases) and in another occupationally exposed matched group (0.79 +/- 0.12 and 1.14 +/-0.14, P < 0.03 and P < 0.01, respectively). The discrepancies observed between the physically recorded doses and the biologically estimated doses indicate that the radiologists did not always wear their dosimeters or that the dosimeters were not always in the radiation field.

Use of risk projection models to estimate mortality and incidence from radiation-induced breast cancer in screening programs.

The authors report on a method to calculate radiological risks, applicable to breast screening programs and other controlled medical exposures to ionizing radiation. In particular, it has been applied to make a risk assessment in the Valencian Breast Cancer Early Detection Program (VBCEDP) in Spain. This method is based on a parametric approach, through Markov processes, of hazard functions for radio-induced breast cancer incidence and mortality, with mean glandular breast dose, attained age and age-at-exposure as covariates. Excess relative risk functions of breast cancer mortality have been obtained from two different case-control studies exposed to ionizing radiation, with different follow-up time: the Canadian Fluoroscopy Cohort Study (1950--1987) and the Life Span Study (1950--1985 and 1950--1990), whereas relative risk functions for incidence have been obtained from the Life Span Study (1958--1993), the Massachusetts tuberculosis cohorts (1926--1985 and 1970--1985), the New York post-partum mastitis patients (1930--1981) and the Swedish benign breast disease cohort (1958--1987). Relative risks from these cohorts have been transported to the target population undergoing screening in the Valencian Community, a region in Spain with about four and a half million inhabitants. The SCREENRISK software has been developed to estimate radiological detriments in breast screening. Some hypotheses corresponding to different screening conditions have been considered in order to estimate the total risk associated with a woman who takes part in all screening rounds. In the case of the VBCEDP, the total radio-induced risk probability for fatal breast cancer is in a range between [5 x 10(-6), 6 x 10(-4)] versus the natural rate of dying from breast cancer in the Valencian Community which is 9.2 x 10(-3). The results show that these indicators could be included in quality control tests and could be adequate for making comparisons between several screening programs.

Modelling of the mammographic exposure conditions for radiological detriment study in the Valencian Breast Cancer Screening Programme.

Breast screening programmes are the best weapon to fight against breast cancer. Nevertheless, despite the benefits, this practice supposes a radiological risk that cannot be forgotten. In order to calculate breast glandular doses, different MCNP-4C2 models have been developed, simulating the exposure conditions. Radiological detriments have been transported from the population under study in the UNSCEAR 2000 to the Valencian Community, obtaining the detection-induced cancer ratio (DICR) for this population.

Declassification of radioactive liquid wastes generated in radio immune assay [corrected] (RIA) laboratories.

Radioactive liquid wastes of low-medium activity level are generated in radio immune assay (RIA) laboratories, which are also potentially infectious because of the pathogens from patient blood. The most common way of managing these wastes consists of a temporal storage, for partial radioactivity decay, followed by management by an authorised company. The object of this work is to study the viability of treating radioactive liquid wastes coming from RIA using membrane techniques in order to reduce their volume, which would mean an improvement from the radiological point of view and a decrease in management costs. This paper describes the results of some experiments carried out with RIA real wastes, by means of processes such as ultrafiltration and reverse osmosis. It has been proved that waste volume can be significantly reduced, obtaining a treated liquid that is free of pathogens and organic matter and with an activity level around the environmental background.

Assessment of mammography spectra using compton spectrometry techniques.

The quality control of mammography units is necessary to reduce the dose imparted to women as much as possible. An accurate characterisation of the primary X-ray spectra is very useful for this purpose. Primary spectra can be obtained using Compton spectrometry techniques. In this work, a commercial spectrometer used to characterise a mammography X-ray tube has been simulated using the Monte Carlo method by means of the MCNP code. Using the developed model, a Response matrix is obtained. Owing to the fact that this matrix is ill-conditioned, the inversion is not a simple process. This problem has been solved using the truncated singular value decomposition method. Results obtained when this methodology was applied have been compared with theoretical X-ray spectra.

A comparative study of computer assisted assessment of image quality index for mammographic phantom images.

Mammographic phantom images are usually used to study the quality of images obtained by dedicated mammographic equipment. The digital image treatment techniques allow us to carry out an automatic analysis of the phantom image. In this work, some techniques of digital image processing are applied to compute a specific image quality index (IQI) for a mammographic phantom, namely CIRS model 11A version SP01. The algorithm designed analyses the phantom image by means of automatic detection of the number of microcalcifications, and the image resolution as the number of line pairs per millimetre. Then, the IQI is calculated from a scoring system. The manner in which the functioning conditions (kV and mAs) of the mammographic equipment and the preprocessing denoising method of the digital image affect the results for the IQI are also studied.

Automatic evaluation of the image quality of a mammographic phantom.

In this work a method has been developed to analyse the digital image quality of a mammographic phantom by means of automatic process techniques. The techniques used for the digital image treatment are standard techniques as the image thresholding to detect objects, the regional growing for pixels pooling and the morphological operator application to determine the objects shape and size, etc. This study allows the obtention of information about the phantom characteristics, that due to its small size and lowly contrast can be obtained very difficultly by direct observation. The final aim of this work is to obtain one or more parameters to characterize the reference phantom quality image in an objective way. These parameters will serve to compare images obtained at different mammographic centers and also, to study the temporal evolution of the image quality produced by determined mammographic equipment.