High-definition FT-IR reveals a synergistic effect on lipid accumulation in prostate cancer cells induced by a combination of X-rays and radiosensitizing drugs.

Radiotherapy is one of the most commonly used cancer therapies with many benefits including low toxicity to healthy tissues. However, a major problem in radiotherapy is cancer radioresistance. To enhance the effect of this kind of therapy several approaches have been proposed such as the use of radiosensitizers. A combined treatment of radiotherapy and radiosensitizing drugs leads to a greater effect on cancer cells than anticipated from the addition of both responses (synergism). In this study, high-definition FT-IR imaging was applied to follow lipid accumulation in prostate cancer cells as a response to X-ray irradiation, radiosensitizing drugs, and a combined treatment of X-rays and the drugs. Lipid accumulation induced in the cells by an increasing X-ray dose and the presence of the drugs was analyzed using Principal Component Analysis and lipid staining. Finally, the synergistic effect of the combined therapy (X-rays and radiosensitizers) was confirmed by calculations of the integral intensity of the 2850 cm-1 band.

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma.

Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model (Mus musculus SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity.

Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures.

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.

Influence of Heat Treatment of Electrospun Carbon Nanofibers on Biological Response.

The main aim of this study is to investigate the effect of fragmentation of electrospun carbon nanofibers (eCNFs) obtained at different temperatures, i.e., at 750 °C, 1000 °C, 1500 °C, 1750 °C and 2000 °C on the cellular response in vitro. In order to assess the influence of nanofibers on biological response, it was necessary to conduct physicochemical, microstructural and structural studies such as SEM, XPS, Raman spectroscopy, HRTEM and surface wettability of the obtained materials. During the in vitro study, all samples made contact with the human chondrocyte CHON-001 cell lines. The key study was to assess the genotoxicity of eCNFs using the comet test after 1 h or 24 h. Special attention was paid to the degree of crystallinity of the nanofibers, the dimensions of the degradation products and the presence of functional groups on their surface. A detailed analysis showed that the key determinant of the genotoxic effect is the surface chemistry. The presence of nitrogen-containing groups as a product of the decomposition of nitrile groups has an influence on the biological response, leading to mutations in the DNA. This effect was observed only for samples carbonized at lower temperatures, i.e., 750 °C and 1000 °C. These results are important with respect to selecting the temperature of thermal treatment of eCNFs dedicated for medical and environmental functions due to the minimization of the genotoxic effect of these materials.

Genotoxicity Associated with 131I and 99mTc Exposure in Nuclear Medicine Staff: A Physical and Biological Monitoring Study.

Nuclear medicine staff are constantly exposed to low doses of ionizing radiation. This study investigated the level of genotoxic effects in hospital employees exposed to routinely used 131I and 99mTc in comparison with a control group. The study compared the results of physical and biological monitoring in peripheral blood lymphocytes. The effects of confounding factors, such as smoking status and physical activity, were also considered. Physical dosimetry monitoring revealed differences in the individual annual effective dose as measured by finger ring dosimeter and whole-body dosimeter between the 131I- and 99mTc-exposed groups. The DNA damage studies revealed differences between the groups in terms of excess premature chromosome condensation (PCC) fragments and tail DNA. Physical activity and smoking status differentiated the investigated groups. When assessed by the level of physical activity, the highest mean values of tail DNA were observed for the 99mTc group. When assessed by work-related physical effort, excess PCC fragments were significantly higher in the 131I group than in the control group. In the investigated groups, the tail DNA values were significantly different between non-smokers and past or current smokers, but excess PCC fragments did not significantly differ by smoking status. It is important to measure exposure to low doses of ionizing radiation and assess the potential risk from this exposure. Such investigations support the need to continue epidemiological and experimental studies to improve our understanding of the mechanisms of the health effects of radionuclides and to develop predictive models of the behavior of these complex systems in response to low-dose radiation.

ATM and RAD51 Repair Pathways in Human Lymphocytes Irradiated with 70 MeV Therapeutic Proton Beam.

The repair of radiation-induced DNA damage is a key factor differentiating patients in terms of the therapeutic efficacy and toxicity to surrounding normal tissue. Proton energy substantially determines the types of cancers that can be treated. The present work investigated the DNA double-strand break repair systems, represented by phosphorylated ATM and Rad51. The status of proton therapy energy used to treat major types of cancer is summarized. Here, human lymphocytes from eight healthy donors (male and female) were irradiated with a spread-out Bragg peak using a therapeutic 70 MeV proton beam or with reference X rays. For both types of radiation, the kinetics of pATM and Rad51 repair protein activation (0-24 h) were estimated as determinants of homologous and non-homologous double-strand break repair. Additionally, γ-H2AX was used as the gold standard marker of double-strand breaks. Our results showed that at 30 min postirradiation there was significantly greater accumulation of γ-H2AX (0.6-fold), pATM (2.0-fold), and Rad51 (0.6-fold) in the proton-irradiated cells compared with the X-ray-treated cells. At 24 h post irradiation, for both types of radiation and all investigated proteins, the foci number was still significantly higher when compared with control. Furthermore, the mean value of pATM and Rad51 repair effectiveness was higher in cells exposed to protons than in cells exposed to X rays; however, the difference was significant only for pATM. The largest inter-individual differences in the repair capabilities were noted for Rad51. The association between the frequency of repair protein foci and the frequency of lymphocyte viability at 1 h post irradiation showed a positive correlation for protons but a negative correlation for X rays. These findings indicate that the accumulation of radiation-induced repair protein foci after proton versus X-ray irradiation differs between patients, consequently affecting the cellular responses to particle therapy and conventional radiation therapy.

Surface Modification of Carbon Nanofibers to Improve Their Biocompatibility in Contact with Osteoblast and Chondrocytes Cell Lines.

The goal of this study is to investigate the influence of different types of modifiers, such as sodium hyaluronate (NaH), graphene oxide (GO), silica oxycarbide (SiOC) and oxidation process (ox) on physicochemical, morphological, and biological properties of electrospun carbon nanofibers (eCNFs). Scanning electron microscopy, X-ray photoelectron spectroscopy and infrared spectroscopy (FTIR) were used to evaluate the microstructure and chemistry of as-prepared and modified CNFs. The electrical properties of CNFs scaffolds were examined using a four-point probe method to evaluate the influence of modifiers on the volume conductivity and surface resistivity of the obtained samples. The wettability of the surfaces of modified and unmodified CNFs scaffolds was also tested by contact angle measurement. During the in vitro study all samples were put into direct contact with human chondrocyte CHON-001 cells and human osteosarcoma MG-63 cells. Their viability was analysed after 72 h in culture. Moreover, the cell morphology and cell area in contact with CNFs was observed by means of fluorescence microscopy. The obtained results show great potential for the modification of CNFs with polymer, ceramic and carbon modifiers, which do not change the fiber form of the substrate but significantly affect their surface and volume properties. Preliminary biological studies have shown that the type of modification of CNFs affects either the rate of increase in the number of cells or the degree of spreading in relation to the unmodified sample. More hydrophilic and low electrically conductive samples such as CNF_ox and CNF_NaH significantly increase cell proliferation, while other GO and SiOC modified samples have an effect on cell adhesion and thus cell spreading. From the point of view of further research and the possibility of combining the electrical properties of modified CNF scaffolds with electrical stimulation, where these scaffolds would be able to transport electrical signals to cells and thus affect cell adhesion, spreading, and consequently tissue regeneration, samples CNF_GO and CNF_SiOC would be the most desirable.

Exploring subcellular responses of prostate cancer cells to clinical doses of X-rays by Raman microspectroscopy.

Modern techniques of radiotherapy such as fractioned radiotherapy require applications of low doses of ionizing radiation (up to 10 Gy) for effective patient treatment. It is, therefore, crucial to understand the response mechanisms in cancer cells irradiated with low (clinical) doses. The cell's response to irradiation depends on a dose and post-irradiation time. Both factors should be considered when studying the influence of ionizing radiation on cancer cells. Thus, in the present study, PC-3 prostate cancer cells were irradiated with clinical doses of X-rays to determine dose- and time-dependent response to the irradiation. Raman spectroscopy and biological methods (MTT and comet assays) were applied for the analysis of biochemical changes in the cells induced by low doses of X-ray irradiation at 0 h and 24 h post-irradiation timepoints. Due to a limited view of the biochemical changes at the subcellular level given by single spectrum Raman measurements, Raman mapping of the whole cell area was performed. The results were compared with those obtained for cell irradiation with high doses. The analysis was based on the Partial Least Squares Regression (PLSR) method for the cytoplasmic and nuclear regions separately. Additionally, for the first time, irradiation classification was performed to confirm Raman spectroscopy as a powerful tool for studies on cancer cells treated with clinical doses of ionizing radiation.

Gold Nanopeanuts as Prospective Support for Cisplatin in Glioblastoma Nano-Chemo-Radiotherapy.

Herein, we propose newly designed and synthesized gold nanopeanuts (Au NPes) as supports for cisplatin (cPt) immobilization, dedicated to combined glioblastoma nano-chemo-radiotherapy. Au NPes offer a large active surface, which can be used for drugs immobilization. Transmission electron microscopy (TEM) revealed that the size of the synthesized Au NPes along the longitudinal axis is ~60 nm, while along the transverse axis ~20 nm. Raman, thermogravimetric analysis (TGA) and differential scanning calorimetry (DCS) measurements showed, that the created nanosystem is stable up to a temperature of 110 °C. MTT assay revealed, that the highest cell mortality was observed for cell lines subjected to nano-chemo-radiotherapy (20-55%). Hence, Au NPes with immobilized cPt (cPt@AuNPes) are a promising nanosystem to improve the therapeutic efficiency of combined nano-chemo-radiotherapy.

Physicochemical damage and early-stage biological response to X-ray radiation studied in prostate cancer cells by Raman spectroscopy.

Exposure to ionizing radiation significantly affects biochemistry of cancer cells. The effect of irradiation can be divided into two stages, that is, the physicochemical stage and the biological response. Both effects induce different biochemical changes in the cells and should be analyzed as two separate phenomena. Thus, in the current study, Raman spectroscopy of prostate cancer cells fixed before (the physicochemical damage model) and just after (the biological response model) irradiation was undertaken to compare biochemical composition of irradiated cancer cells at both stages. Spectroscopic analysis of the cells was performed separately for cytoplasmic and nuclear regions. Biochemical changes of irradiated cells were analyzed using partial least squares regression (PLSR) method on the basis of the collected Raman spectra. Regression coefficients were therefore used to describe differences and similarities between biochemical composition of cancer cells undergoing the physicochemical stage and biological response. Additionally, PLSR models of both phenomena were compared for linear dose-dependence and a cross prediction.

Lipid droplets in prostate cancer cells and effect of irradiation studied by Raman microspectroscopy.

Lipid droplets (LDs) are key organelles in cancer cells proliferation, growth, and response to stress. These nanometric structures can aggregate to reach the size of microns becoming important cell components. Although it is known that LDs contain various lipids, their chemical composition is still under investigation. Moreover, their function in cell's response to exogenous factors is also not fully understood. Raman spectroscopy, together with chemometrics, has been shown to be a powerful tool for analytical analyses of cancer cell components on the subcellular level. It provides the opportunity to analyse LDs in a label-free manner in live cells. In the current study, this method was applied to investigate LDs composition in untreated and irradiated with X-ray beams prostate cancer cells. Raman mapping technique proved lipids accumulation in PC-3 cells and allowed visualization of LDs spatial distribution in cytoplasm. A heterogeneous composition of LDs was revealed by detailed analysis of Raman spectra. Interestingly, PC-3 cells were found to accumulate either triacylglycerols or cholesteryl esters. Finally, effect of X-ray radiation on the cells was investigated using Raman spectroscopy and fluorescence staining. Significant influence of LDs in the process of cell response was confirmed and time dependence of this phenomenon was determined.

Assessment of the nuclear medicine personnel occupational exposure to radioiodine.

PURPOSE: To physically and cytogenetically screen medical personnel of Department of Endocrinology and Nuclear Medicine, Holy Cross Cancer Center, Kielce, Poland (DENM) who are occupationally exposed to 131I. MATERIALS AND METHODS: The exposure was monitored by whole-body and finger ring dosimeters. The thyroid iodine intake was measured by a whole-body spectrometer equipped with two semiconductor gamma radiation detectors. A cytokinesis-block micronucleus assay and the premature chromosome condensation technique were used to assess the aberration score. Cytogenetic analyses were carried out on a group of 29 workers and were compared to 32 controls (healthy donors), matched for gender and age. RESULTS: On average, the exposed group showed a significantly higher frequency of genetic damage and a higher proliferation index compared to the control group. Smoking status, age and duration of exposure influenced the observed effects in both groups. No differences in measured biomarkers were observed after stratification of the exposed group into two subgroups based on the measured 131I activity below and above 6 Bq. CONCLUSION: The findings suggest that radiation protection principles based on whole-body and finger ring dosimetry, supported by activity measurements with a whole-body spectrometer, may be insufficient to monitor the absorbed dose estimation of the nuclear medicine staff who are occupationally exposed to 131I. Furthermore, their future health risks are influenced by confounders. Direct assessments comparing physical and biological dose estimations on the larger group are needed to accurately monitor occupational radiation exposure.

Nanoscale AFM-IR spectroscopic imaging of lipid heterogeneity and effect of irradiation in prostate cancer cells.

The recent development of the AFM-IR technique, which combines nanoscale imaging with chemical contrast through infrared spectroscopy, opened up new fields for exploration, which were out of reach for other modalities, e.g. Raman spectroscopy. Lipid droplets (LDs) are key organelles, which are associated with stress response mechanisms in cells and their size falls into that niche. LDs composition is heterogeneous and varies depending on cancer cell type and the tumor microenvironment. Prostate cancer cells show a unique lipid metabolism manifested by an increased requirement for lipid accumulation in cytosolic LDs. In the current work, AFM-IR nanoimaging was undertaken to analyze lipids in untreated and x-ray irradiated PC-3 prostate cancer cells. Cells poor in LDs showed slightly increased lipid signal in cytoplasm close to the nucleus. On the other hand, high lipid signal coming from LDs accumulation could be found in any part of the cytoplasmic region. The observed behavior was found to be independent from irradiation and its dose. According to the band assignment of the collected AFM-IR spectra, the main components of LDs were assigned to cholesteryl esters. The size of LDs present in cells poor in lipids was found to be of less than 1 µm, whereas LDs aggregates spread out over a few microns. Analysis of AFM-IR spectra shows relative homogeneity of LDs composition in single cells and heterogeneity of LDs content within the PC-3 cell population.

Exploring subcellular responses of prostate cancer cells to X-ray exposure by Raman mapping.

Understanding the response of cancer cells to ionising radiation is a crucial step in modern radiotherapy. Raman microspectroscopy, together with Partial Least Squares Regression (PLSR) analysis has been shown to be a powerful tool for monitoring biochemical changes of irradiated cells on the subcellular level. However, to date, the majority of Raman studies have been performed using a single spectrum per cell, giving a limited view of the total biochemical response of the cell. In the current study, Raman mapping of the whole cell area was undertaken to ensure a more comprehensive understanding of the changes induced by X-ray radiation. On the basis of the collected Raman spectral maps, PLSR models were constructed to elucidate the time-dependent evolution of chemical changes induced in cells by irradiation, and the performance of PLSR models based on whole cell averages as compared to those based on average Raman spectra of cytoplasm and nuclear region. On the other hand, prediction of X-ray doses for individual cellular components showed that cytoplasmic and nuclear regions should be analysed separately. Finally, the advantage of the mapping technique over single point measurements was verified by a comparison of the corresponding PLSR models.

Increased elasticity of melanoma cells after low-LET proton beam due to actin cytoskeleton rearrangements.

Cellular response to non-lethal radiation stress include perturbations in DNA repair, angiogenesis, migration, and adhesion, among others. Low-LET proton beam radiation has been shown to induce somewhat different biological response than photon radiation. For example, we have shown that non-lethal doses of proton beam radiation inhibited migration of cells and that this effect persisted long-term. Here, we have examined cellular elasticity and actin cytoskeleton organization in BLM cutaneous melanoma and Mel270 uveal melanoma cells. Proton beam radiation increased cellular elasticity to a greater extent than X-rays and both types of radiation induced changes in actin cytoskeleton organization. Vimentin level increased in BLM cells after both types of radiation. Our data show that cell elasticity increased substantially after low-LET proton beam and persisted long after radiation. This may have significant consequences for the migratory properties of melanoma cells, as well as for the cell susceptibility to therapy.

Neutrophil-to-lymphocyte ratio predicts long-term all-cause mortality in patients with chronic kidney disease stage 5.

INTRODUCTION: A high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a strong biomarker of inflammation. AIM: We sought to evaluate the impact of NLR on long-term all-cause and cardio-vascular (CV) mortality in hemodialysis (HD) patients. MATERIAL AND METHODS: total of 84 chronic kidney disease (CKD) stage 5 patients with 54 of them on HD, with a median age of 61.5 (51.3-74.8) years were enrolled. e association between NLR and clinical biomarkers was investigated. Multivariable Cox regression analysis was used to find significant predictors of all-cause and CV mortality at follow-up. RESULTS: the median NLR (interquartile range) was 3.0 (2.1-4.1). Patients with NLR ≥3.9 (the highest tertile) had higher five-year all-cause mortality then remaining patients (53.6% vs. 30.4%; p = 0.039). On the contrary, only a trend towards increased CV mortality was observed (25.0% vs. 42.9%; p = 0.10). NLR ≥3.9 was a significant predictor of all-cause mortality at five years [hazard ratio (95%CI): 2.23 (1.10-4.50); p = 0.025] in Cox regression model adjusted for age, gender, and diabetes status. Similarly, while using NLR as continuous variable a significant association between NLR and all-cause mortality was confirmed even a er adjustment for covariates [hazard ratio per 1 unit increase (95%CI): 1.26 (1.06-1.51); p = 0.009] with the area under the receiver operating characteristic (ROC) curve of 0.64. Correlations between NLR and WBC, concentration of fibrinogen, albumin were observed. CONCLUSIONS: Asymptomatic inflammation measured by NLR showed an association with long-term all-cause mortality in stage 5 CKD patients, even while white blood cell count was in the normal range.

Biological effects and inter-individual variability in peripheral blood lymphocytes of healthy donors exposed to 60 MeV proton radiotherapeutic beam.

Purpose: The aim of our study was to investigate the amount of initial DNA damage and cellular repair capacity of human peripheral blood lymphocytes exposed to the therapeutic proton beam and compare it to X-rays. Materials and methods: Lymphocytes from 10 healthy donors were irradiated in the Spread Out Bragg Peak of the 60 MeV proton beam or, as a reference, exposed to 250 kV X-rays. DNA damage level was assessed using the alkaline version of the comet assay method. For both sources of radiation, dose-DNA damage response (0-4 Gy) and DNA repair kinetics (0-120 min) were estimated. The observed DNA damage was then used to calculate the relative biological effectiveness (RBE) of the proton beam in comparison to that of X-rays. Results: Dose-response relationships for the DNA damage level showed linear dependence for both proton beam and X-rays (R2 = 0.995 for protons and R2 = 0.993 for X-rays). Within the dose range of 1-4 Gy, protons were significantly more effective in inducing DNA damage than were X-rays (p < .05). The average RBE, calculated from the proton and X-ray doses required for the iso-effective, internally standardized tail DNA parameter (sT-DNA) was 1.28 ± 0.57. Similar half-life time of residual damage and repair efficiency of induced DNA damage for both radiation types were observed. In the X-irradiated group, significant inter-individual differences were observed. Conclusions: Proton therapy was more effective at high radiation doses. However, DNA damage repair mechanism after proton irradiation seems to differ from that following X-rays.

Response of human lymphocytes to proton radiation of 60 MeV compared to 250 kV X-rays by the cytokinesis-block micronucleus assay.

Particle radiotherapy such as protons provides a new promising treatment modality to cancer. However, studies on its efficacy and risks are relatively sparse. Using the cytokinesis-blocked micronucleus assay, we characterized response of human peripheral blood lymphocytes, obtained from health donors irradiated in vitro in the dose range: 0-4. 0 Gy, to therapeutic proton radiation of 60 MeV from AIC-144 isochronous cyclotron, by studying nuclear division index and DNA damage and compared them with X-rays. Peripheral blood lymphocytes show decreased ability to proliferate with increasing radiation doses for both radiation types, however, in contrast to X-rays, irradiation with protons resulted in a higher proliferation index at lower doses of 0.75 and 1.0 Gy. Protons are more effective in producing MN at doses above 1.75 Gy compared to X-rays. Dose-response curves for micronucleus incidence can be best described by a cubic model for protons, while for X-rays the response was linear. The differences in the energy spectrum and intracellular distribution of energy between radiation types are also apparent at the intracellular distribution of cytogenetic damage as seen by the distribution of various numbers of micronuclei in binucleated cells. Our studies, although preliminary, further contribute to the understanding of the mechanistic differences in the response of HPBL in terms of cellular proliferation and cytogenetic damage induced by protons and X-rays as well as intra-cellular distribution of energy and thus radiobiological effectiveness.

[Goodpasture's syndrome--disease of many faces]. / Zespól Goodpasture'a - choroba o wielu obliczach.

Pulmonary-renal syndrome (PRS) can originate from several connective tissue diseases. It belongs to the potentially life-threatening conditions. Clinically PRS is a combination of diffuse pulmonary hemorrhage and renal involvement including glomerulonephritis, nephrotic syndrome or acute renal failure. Goodpasture's syndrome accounts for approximately 20% cases of PRS. Until recently diffuse pulmonary hemorrhage connected with rapid progressive glomerulonephritis usually resulted in a very bad prognosis. However now, rapid diagnostic process (antibodies identification, kidney and pulmonary biopsy) can speed up a difficult decision of using intense immunosuppressive therapy including cyclophosphamide and methylprednisolone pulses or plasma exchanges. Simultaneously, the therapy should be supported by artificial ventilation and renal replacement therapy. In some cases such a treatment can be followed by a complete recovery from renal and pulmonary diseases. The combined therapy contributed to considerable reduction in mortality rate that recently has been achieved in PRS patients. In present paper 3 cases of Goodpasture's syndrome with different manifestations of the disease were described.

Exposure to environmental polycyclic aromatic hydrocarbons: influences on cellular susceptibility to DNA damage (sampling Kosice and Sofia).

The aim of this study was to investigate a possible influence of occupational exposure to carcinogenic environmental polycyclic aromatic hydrocarbons (c-PAHs) on cellular susceptibility to the induction of the DNA damage. Monitoring was performed and blood samples were collected from two groups of male subjects: occupationally exposed and matched controls. The group exposed to c-PAHs (average age of 35.1 years) consisted of 52 policemen from Kosice and 26 policemen and 25 bus drivers (51 altogether) from Sofia. The control group (average age of 36.4 years) consisted of 54 unexposed subjects from Kosice and 24 from Sofia. In the investigated groups 52.5% of exposed subjects and 45.3% of control were current smokers. A challenging dose of X-rays (3Gy) and an alkaline version of the single cell gel electrophoresis (SCGE) assay, known as Comet assay, were used to evaluate levels of induced DNA damage and repair kinetics in isolated human blood lymphocytes. DNA damage detected in lymphocytes prior to or after irradiation did not differ significantly between exposed and unexposed subjects. A significant decrease in repair efficiency due to exposure to PAHs was observed in the exposed individuals from Kosice and Sofia, when analysed separately or together. A negative influence of tobacco smoking on the efficiency of DNA repair was observed. Statistically significant differences were found between subgroups stratified according to education level in Sofia: the half times for DNA repair declined with the increasing level of education. These results confirm that environmental exposure to c-PAHs can alter the ability of blood lymphocytes to repair DNA damage and, as a result could potentially lead to effects that are hazardous to human health.