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Abstract: Osteopontin (OPN) is one of the major non-collagen proteins in extracellular bone matrix. To elucidate the function of OPN in bone metabolism, a cellular defect was created in parietal bone and tibia of 12 rats. In Group 1, the left defects were filled with OPN-coated hydroxyapatite (OPN-H). In Group 2, the right defects were filled with non-coated hydroxyapatite (N-H). In both groups, the contra lateral defects were used as control defects. In Group 3, OPN-H was inserted in the left defects and N-H in the right defects. Bone metabolism was measured by 45Ca and technetium-99m methylene diphosphonate scintigraphy for 4 weeks. Scintigraphy did not show any significant differences in bone metabolism between the defects filled with OPN-H and N-H. A higher bone metabolism was measured between the parietal defects filled with OPN-H or N-H in comparison with the parietal control defects. This difference, however, was not significant and was less for tibia defects. Histological observation (7th week) shows less inflammatory cells at the tibia defects filled with OPN-H compared to the tibia defects filled with N-H. This study did not show any acceleration or inhibition of bone metabolism in parietal or tibia bone in rats, but there is some evidence that OPN might influence inflammatory cells in bone matrix. [Copyright &y& Elsevier]

In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3.5 Gy Co γ-rays and for the G2 assay PHA stimulated cultures were irradiated with a dose of 0.4 Gy Co γ-rays in the G2 phase of the cell cycle. For 14 donors, 2–15 repeat samples were tested over a period of 3 years. The repeat experiments revealed that the intra-individual variability was not significantly different from the inter-individual variability for both G2 and MN assays. As the intra-individual variability determines the reproducibility of the assay, our results highlight the limitations of these endpoints in detecting reproducible differences in radiation sensitivity between individuals within a normal population.Due to the high intra-individual variability and no significant difference with the inter-individual variability found in our study we conclude that care has to be taken when results obtained with chromosomal aberration assays based on one blood sample are used to assess the individual radiosensitivity. Multiple blood sampling may be necessary to draw reliable conclusions. Although more validation studies on the reliability of the G2 and MN assay will be required before they can be used in a confident way as biomarkers of individual radiosensitivity or cancer susceptibility the assays are very valuable to examine population radiosensitivity and the relationship between radiosensitivity, cancer predisposition and genotype. [Copyright &y& Elsevier]

Introduction Radiation is known to be an inducer of cancer, however, radiation is also often used in a useful manner in radiotherapy and diagnostic imaging. In this research, we investigated the efficiency of different radiation qualities to induce DNA damage and how this damage is repaired by different cell types. Material and methods Lymphocytes, MCF-10A cells and epithelial cells in resected breast tissue were irradiated with high LET fast neutrons and low LET 30 kV X-rays and 1.2 MeV 60 Co γ -rays. By means of the γ H2AX-foci assay we analyzed the efficiency in DNA DSB-induction by the different radiation qualities. With the micronucleus (MN) assay we analyzed how efficient these DSB, induced by different radiation qualities, were repaired by the cell. Results While a lower number of radiation-induced γ H2AX-foci was observed for neutron radiation compared to γ -rays until about 4h post-IR, foci repair was slower and more residual foci were present at later time points. Furthermore, neutrons seem to be more effective in inducing MN. Irradiation of human lymphocytes with 30kV X-rays resulted in a modest increase in the number of γ H2AX-foci compared to γ -rays, but these DSB were more difficult to repair correctly by the cell and resulted in a more pronounced increase in MN compared to γ -rays. Furthermore, in the 0–20 mGy dose-range a low-dose hypersensitive response for DSB induction was observed in mammary epithelial cells present in resected breast tissue, probably caused by the bystander effect. Conclusion These results are important to assess the effects of radiotherapy and may have important implications for the risk assessment of mammography screening. [ABSTRACT FROM AUTHOR]

Introduction About 5% of cancer patients receiving radiation therapy (RT) exhibit severe normal tissue reactions. The prediction of late toxicity in cancer patients would enable individualized and optimized radiation dose prescription. In this study, four different candidate in vitro cellular radiosensitivity assays for prediction of late normal tissue reactions were evaluated in a retrospective matched case-control set-up of breast cancer patients. Materials and methods Breast cancer patients expressing severe radiation toxicity (12 cases) and no or minimal reactions (12 controls) with a follow-up of at least 3 years were selected for this study. Case and control patients were matched for therapy and patient related variables. After in vitro irradiation of patient blood samples, case and control radiation responses were compared for the following biological end points: radiation-induced CD8+ late apoptosis, residual DNA double strand breaks (DSB), G0 and G2+caf micronucleus assay. Results Despite a substantial overlap in standard deviations, all cellular assays showed a significant difference between cases and controls. Less radiation-induced apoptosis was observed in CD8+ lymphocytes of cases (14.45%) compared to the matched controls (30.64%) ( p < 0.01). The number of residual DNA DSB was higher in cases (9.92 foci/cell) compared to their matched controls (9.17 foci/cell) ( p < 0.01). The average dose response curve of the G0 MN assay for cases lies above the average dose response curve of the controls. Finally, a pairwise comparison of the G2+caf MN results showed a higher MN yield for cases (351 MN/1000BN) compared to controls (219 MN/1000BN) ( p < 0.01). Conclusion Current results suggest that intrinsic radiosensitivity is involved in the development of late radiotoxic effects. Larger prospective studies are warranted to validate the retrospective findings in order to use in vitro cellular assays in the future to predict late normal tissue radiosensitivity in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction Radiological health concerns for individuals exposed to ionizing radiation are governed by both the extent of exposure, as well as the microscopic dose distribution of the radiation modality. Several quantitative biological endpoints have been developed for radiation dose estimation and are employed worldwide. For real world biodosimetry applications, qualitative aspects such as the radiation type and homogeneity of exposure are vital in the decision making process with respect to suitable medical interventions. Materials and methods Whole blood samples collected from two consenting adults were exposed to 60 Co γ -rays to doses ranging from 1–6 Gy and 0–2 Gy p(66)/Be neutrons. The samples exposed to 60 Co γ -rays were subsequently diluted with un-irradiated blood to yield a series of equivalent total body doses (ETBD) from 0 up to 4 Gy. Dicentric formation frequencies in T-lymphocyte metaphase spreads were enumerated with the aid of a semi-automated image analysis microscopy system. Results Dicentric formation induction frequencies were used to estimate whole body doses for each sample respectively. Estimated whole body doses where compared to the equivalent total body dose (ETBD) and found to be in agreement (Pearson’s ρ 0.97 < p < 0.99). Furthermore the distribution of cytogenetic effects amongst cells within each sample was used to calculate dispersion indices. Similarly to heterogeneous exposures, where damage events appear to be grouped in a specific subpopulation of cells, samples exposed to high-LET radiation also align to this trend. The intercellular distribution of dicentric aberrations for heterogeneously exposed samples ( σ 2 / y ¯ ≥ 1.2 ) and high LET neutron samples ( σ 2 / y ¯ ≈ 1.2 ) were found to be over-dispersed assuming a Poisson distribution applies to the induction of dicentric formations in cells. Conclusion The dispersion parameter proves to be a useful addition to the dicentric chromosome assay to ascertain qualitative aspects of the exposure conditions required for effective population triage for samples analysed with the high throughput automated image analysis system. [ABSTRACT FROM AUTHOR]

Introduction Due to their long life span, accumulation of DNA damage in stem cells can compromise their genomic integrity. Hematopoietic stem and progenitor cells (HSPCs), characterized by the cell surface marker CD34, may be a major target for radiation-induced leukemogenesis. Secondary leukemia risks are especially important for childhood cancer survivors treated with radiotherapy, since epidemiological data indicate that the risk for radiation-induced hematological malignancies is 3–5 times higher for children compared to adults. In order to investigate the underlying mechanism of radiation-induced leukemia, an in vitro study of the radiation effects in CD34+ cells was performed. Materials and Methods Human CD34+ HSPCs were isolated from umbilical cord blood by using CD34+ immunomagnetic beads (Miltenyi). Peripheral blood T-lymphocytes were isolated from healthy adults using RosetteSep TM human T-cell enrichment cocktail (Stemcell). Radiation-induced DNA double-strand breaks (DSBs) were assessed by microscopic scoring of γ -H2AX/53BP1 foci 0.5h after low-dose x-ray exposure, while DNA repair was evaluated by scoring residual γ -H2AX/53BP1 foci 24h after 4 Gy x-ray exposure. A micro-culture cytokinesis block micronucleus (MN) assay was developed for CD34+ cells in order to study radiation-induced mutagenic effects after 2 Gy x-ray exposure. Results HSPCs show significantly lower endogenous levels of DNA DSBs and MNi compared to adult T-lymphocytes. No statistical significant difference could be observed in the number of DNA DSBs induced by low-dose x-rays (100 and 200 mGy) between HSPCs and T-lymphocytes. However, the number of residual DNA DSBs 24h post-exposure was significantly lower in HSPCs (3.54 foci/cell) compared to T-lymphocytes (5.77 foci/cell). Furthermore, HSPCs showed a significantly higher number of MNi (371MN/1000BN cells) compared to T-lymphocytes (275MN/1000BN cells). Conclusion The low number of residual DNA DSBs 24h post-exposure and the high number of radiation-induced MN yields in HSPCs indicate fast error-prone DNA repair and mutagenesis after radiation exposure, which could trigger leukemia development. [ABSTRACT FROM AUTHOR]

Abstract: As dynamic flat-panel detectors (FD) are introduced in interventional cardiology (IC), the relation between patient dose and image quality (IQ) needs to be reconsidered for this type of image receptor. On one hand this study investigates IQ of a FD system by means of a threshold contrast-detail analysis and compares it to an image intensifier (II) system on a similar X-ray setup. On the other hand patient dose for coronary angiography (CA) procedures on both systems is compared by Dose-Area Product (DAP)-registration of a patient population. The comparative IQ study was performed for a range of entrance dose rates (EDR) covering the fluoroscopy and cinegraphy working mode. In addition the IQ investigation was extended to a similar study under automatic brightness control (ABC). As well the systematic study of IQ as a function of EDR as the study performed under ABC point to a better IQ for FD in cinegraphy mode and no difference between both systems in fluoroscopy mode. The patient population study resulted in mean DAP values of 31Gycm2 (II system) and 33Gycm2 (FD system) (p =0.68) for CA procedures. As well total DAP as contributions of fluoroscopy and cinegraphy on both systems are not significantly different. To conclude, we could state that profit was taken from the intrinsic better performance of the FD for cinegraphy mode in producing higher quality images in this mode but without any effect on patient dose for CA procedures. [Copyright &y& Elsevier]