Mitchel, R. E. J., Jackson, J. S., Morrison, D. P. and Carlisle, S. M. Low Doses of Radiation Increase the Latency of Spontaneous Lymphomas and Spinal Osteosarcomas in Cancer-Prone, ...Radiation-Sensitive Trp53 Heterozygous Mice. Radiat. Res. 159, 320–327 (2003). Mice heterozygous for Trp53 are radiation-sensitive and cancer-prone, spontaneously developing a variety of cancer types. Osteosarcomas in the spine lead to paralysis, while lymphomas lead rapidly to death, distinct events that provide objective measures of latency. The effects of a single low-dose (10 or 100 mGy), low-dose-rate (0.5 mGy/min) 60Co γ irradiation on lymphoma or spinal osteosarcoma frequency and latency, defined as time of death or of onset of paralysis, respectively, were examined. Compared to spontaneous lymphomas or to spinal osteosarcomas leading to paralysis in unexposed mice, an exposure of 7–8-week-old Trp53+/− mice to 10 or 100 mGy had no significant effect on tumor frequency, indicating no effect on tumor initiation. All tumors are therefore assumed to be of spontaneous origin. However, a 10-mGy exposure reduced the risk of both lymphomas and spinal osteosarcomas by significantly increasing tumor latency, indicating that the main in vivo effect of a low-dose exposure is a reduction in the rate at which spontaneously initiated cells progress to malignancy. The effect of this adaptive response persisted for the entire life span of all the animals that developed these tumors. Exposure to 100 mGy delayed lymphoma latency longer than the 10-mGy exposure. However, the 100-mGy dose increased spinal osteosarcoma risk by decreasing overall latency compared to unexposed control mice. That result suggested that this higher dose was in a transition zone between reduced and increased risk, but that the dose at which the transition occurs varies with the tumor type.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Apicomplexan parasites harbor a secondary plastid that is essential to their survival. Several metabolic pathways confined to this organelle have emerged as promising parasite-specific drug targets. ...The maintenance of the organelle and its genome is an equally valuable target. We have studied the replication and segregation of this important organelle using the parasite Sarcocystis neurona as a cell biological model. This model system makes it possible to differentiate and dissect organellar growth, fission and segregation over time, because of the parasite's peculiar mode of cell division. S. neurona undergoes five cycles of chromosomal replication without nuclear division, thus yielding a cell with a 32N nucleus. This nucleus undergoes a sixth replication cycle concurrent with nuclear division and cell budding to give rise to 64 haploid daughter cells. Interestingly, intranuclear spindles persist throughout the cell cycle, thereby providing a potential mechanism to organize chromosomes and organelles in an organism that undergoes dramatic changes in ploidy. The development of the plastid mirrors that of the nucleus, a continuous organelle, which grows throughout the parasite's development and shows association with all centrosomes. Pharmacological ablation of the parasite's multiple spindles demonstrates their essential role in the organization and faithful segregation of the plastid. By using several molecular markers we have timed organelle fission to the last replication cycle and tied it to daughter cell budding. Finally, plastids were labeled by fluorescent protein expression using a newly developedS. neurona transfection system. With these transgenic parasites we have tested our model in living cells employing laser bleaching experiments.
In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose–responses in fibroblasts from three ungulate species (white-tailed deer, woodland ...caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1–4 Gy of
60Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1–100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small “adapting” stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sarcocystis neurona, an apicomplexan parasite, is the primary causative agent of equine protozoal myeloencephalitis. Like other members of the Apicomplexa,
S. neurona zoites possess secretory ...organelles that contain proteins necessary for host cell invasion and intracellular survival. From a collection of
S. neurona expressed sequence tags, we identified a sequence encoding a putative microneme protein based on similarity to
Toxoplasma gondii MIC10 (TgMIC10). Pairwise sequence alignments of SnMIC10 to TgMIC10 and NcMIC10 from
Neospora caninum revealed approximately 33% identity to both orthologues. The open reading frame of the
S. neurona gene encodes a 255 amino acid protein with a predicted 39-residue signal peptide. Like TgMIC10 and NcMIC10, SnMIC10 is predicted to be hydrophilic, highly alpha-helical in structure, and devoid of identifiable adhesive domains. Antibodies raised against recombinant SnMIC10 recognised a protein band with an apparent molecular weight of 24 kDa in Western blots of
S. neurona merozoites, consistent with the size predicted for SnMIC10. In vitro secretion assays demonstrated that this protein is secreted by extracellular merozoites in a temperature-dependent manner. Indirect immunofluorescence analysis of SnMIC10 showed a polar labelling pattern, which is consistent with the apical position of the micronemes, and immunoelectron microscopy provided definitive localisation of the protein to these secretory organelles. Further analysis of SnMIC10 in intracellular parasites revealed that expression of this protein is temporally regulated during endopolygeny, supporting the view that micronemes are only needed during host cell invasion. Collectively, the data indicate that SnMIC10 is a microneme protein that is part of the excreted/secreted antigen fraction of
S. neurona. Identification and characterisation of additional
S. neurona microneme antigens and comparisons to orthologues in other Apicomplexa could provide further insight into the functions that these proteins serve during invasion of host cells.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There is a general consensus that 5–25% of schizophrenic patients are partially or totally unresponsive to antipsychotic drug therapy (Brenner et al, 1990). Agreement is needed on how to define the ...varying degrees of response and resistance in individual patients on conventional antipsychotic medication. Apparent “treatment resistance” may be due to noncompliance; excessive protein binding with inadequate bio-availability of the neuroleptic; an inadequate or excessive dose resulting in poor efficacy or side-effects outweighing therapeutic effects (Osser, 1989); or incorrect diagnosis.
Purpose : To carry out a comparative study on potential cytogenetic fingerprints for radiation LET in human metaphase lymphocytes. Materials and methods : Human lymphocytes were irradiated in vitro ...with 3.0Gy 60 Co γ-rays, 0.9 Gy 3 H β -rays or 0.2 Gy 2.7Mev neutrons. Detailed chromosome aberrations were analysed by combined FISH with pan-telomere staining and specific wholechromosome painting (1, 2 and 4). Total chromosome translocations and insertions were also analysed by multicolour wholechromosome painting (chromosomes 1, 2 and 4 orange, chromosomes 3, 5 and 6 green). Results : Among the six proposed radiation cytogenetic fingerprints, the ratio of total simple translocations to insertions (I-ratio), showed the largest difference between low-LET 60Co γ-ray and high-LET neutron radiation. The ratios of complete exchanges to incomplete rejoinings S(I)-ratio and dicentrics to interstitial deletions (H-ratio), showed a similar significant difference between low- and high-LET radiation. The ratios of centric rings to interstitial deletion (G-ratio) showed a trend of LETrelated difference, but the difference was not significant in this data set. The ratios of dicentrics to centric rings (F-ratio) and apparent complete exchanges to hidden complete exchanges S(II)-ratio, showed no difference between low- and high-LET radiation. In the 1426 radiation-induced chromosome aberrations observed after 52h culture, evidence for sister-chromatid fusion but not telomere addition was found. Conclusion : Pan-telomere staining plus specific whole chromosome painting allows simultaneous and objective detection of complete or incomplete chromosome exchanges and interstitial or terminal deletions in human peripheral lymphocytes. Of the six proposed cytogenetic ratios, the I-ratio is the most effective cytogenetic fingerprint for distinguishing low-LET from high-LET radiation in human metaphase human lymphocytes.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
8.
PHENIX on-line and off-line computing Adler, S.S.; Chujo, T.; Desmond, E.J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2003, Volume:
499, Issue:
2
Journal Article
Peer reviewed
Data handling in PHENIX is carried out by the On-Line Computing System (ONCS) and Off-Line Computing System (Off-Line). ONCS provides the overall control and monitoring of the front-end electronics, ...trigger and data acquisition system and detector ancillary systems. It configures and initializes the on-line system, monitors and controls the data flow, coordinates calibration processes, interlocks the data acquisition process with the slow control subsystems and performs a number of other functions. ONCS uses CORBA software to monitor and control the hardware. Off-Line provides all aspects of data handling not directly connected to the collection of data and monitoring, such as event simulation and reconstruction, data analysis and information management. The impact of the unprecedented data volumes on the design is presented, along with a detailed discussion of the tasks and methods of simulating, obtaining and monitoring the data.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Radiation exposures from tritium make up a substantial fraction of the occupational and accidental radiation exposures associated with the nuclear power industry. Tritiated water, the most abundant ...form of tritium, is of particular interest because it is readily taken up by human cells and its irradiation of the cells is spread over a period of days. To approximate the prolonged exposure and the conditions that the cells of an individual would experience in vivo, we irradiated human lymphocytes with tritiated water for 48 h in a 1:1 blood:medium mix. For estimation of the tritium β-ray dose, a cellular water content of 0.78, based on measurements of human lymphoblastoid cells in culture medium, was used. A modified dose calculation formula was developed for the radiation exposure conditions. A total of 48,014 metaphases (14,482 in irradiated samples and 33,532 in control, unirradiated samples) in human lymphocytes cultured for 72 h after exposure were analyzed for chromosome translocations using fluorescence in situ hybridization. The linear slope (α coefficient) of the dose-response curve was measured to be $(3.93\pm 0.42)\times 10^{-2}$ and $(5.26\pm 0.48)\times 10^{-2}$ translocations per cell per gray for complete translocations (tc) and complete translocations plus incomplete translocations ti(Ab), respectively, when the data were fitted to a linear model using a weighted least-squares method. The α coefficient for tc is significantly lower than that for conventionally measured dicentrics after tritium β irradiation, but the α coefficient for tc + ti(Ab) does not differ significantly from that for dicentrics. This is in agreement with theoretical considerations. The importance of scoring criteria is stressed. The frequency of tc + ti(Ab) is proposed to be a reliable biodosimeter for tritium exposures, and its practical use in a dose reconstruction is presented.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We have tested the possibility of using apoptosis (programmed cell death) in human peripheral blood lymphocytes as a short-term biological dosimeter. Lymphocytes isolated from whole blood were ...irradiated in culture with 250 kVp x-rays or 60Co gamma rays. Two assays were used to measure apoptosis in lymphocytes after irradiation: in situ terminal deoxynucleotidyl transferase assay and fluorescence analysis of DNA unwinding assay. Similar qualitative and quantitative results were produced by the assays, supporting the notion that the fluorescence analysis of DNA unwinding assay measured DNA fragmentation associated with apoptosis. Induction of apoptosis in lymphocytes irradiated in vitro was proportional to dose and could be detected following exposures as low as 0.05 Gy. Lymphocytes from individual donors had reproducible dose responses. There was, however, variation between donors. X-ray and gamma-ray exposures induced similar levels of apoptosis at similar doses. The induction kinetics of apoptosis in vitro indicate a maximum is reached about 72 h after irradiation. In conclusion, the in vitro experimental evidence indicates that radiation-induced apoptosis in human lymphocytes has the kinetics, sensitivity, and reproducibility to be a potential biological dosimeter.
PDF
