Contribution of the two dsRBM motifs to the double-stranded RNA binding and protein interactions of PACT.

PACT is a stress-modulated activator of protein kinase PKR (protein kinase, RNA activated), which is involved in antiviral innate immune responses and stress-induced apoptosis. Stress-induced phosphorylation of PACT is essential for PACT's increased association with PKR leading to PKR activation, phosphorylation of translation initiation factor eIF2α, inhibition of protein synthesis, and apoptosis. PACT-induced PKR activation is negatively regulated by TRBP (transactivation response element RNA-binding protein), which dissociates from PACT after PACT phosphorylation in response to stress signals.

Physical and biological organ dosimetry analysis for international space station astronauts.

In this study, we analyzed the biological and physical organ dose equivalents for International Space Station (ISS) astronauts. Individual physical dosimetry is difficult in space due to the complexity of the space radiation environment, which consists of protons, heavy ions and secondary neutrons, and the modification of these radiation types in tissue as well as limitations in dosimeter devices that can be worn for several months in outer space. Astronauts returning from missions to the ISS undergo biodosimetry assessment of chromosomal damage in lymphocyte cells using the multicolor fluorescence in situ hybridization (FISH) technique.

Stability of chromosome aberrations in the blood lymphocytes of astronauts measured after space flight by FISH chromosome painting.

Follow-up measurements of chromosome aberrations in the blood lymphocytes of astronauts were performed by FISH chromosome painting at various intervals from 5 months to more than 5 years after space flight and compared to preflight baseline measurements. For five of the six astronauts studied, the analysis of individual time courses for translocations revealed a temporal decline of yields with half-lives ranging from 10 to 58 months. The yield of exchanges remained unchanged for the sixth astronaut during an observation period of 5 months after flight.

Chromosome aberrations of clonal origin are present in astronauts' blood lymphocytes.

Radiation-induced chromosome translocations remain in peripheral blood cells over many years, and can potentially be used to measure retrospective doses or prolonged low-dose rate exposures. However, several recent studies have indicated that some individuals possess clones of cells with balanced chromosome abnormalities, which can result in an overestimation of damage and, therefore, influence the accuracy of dose calculations. We carefully examined the patterns of chromosome damage found in the blood lymphocytes of twelve astronauts, and also applied statistical methods to screen for the presence of potential clones.

In vivo and in vitro measurements of complex-type chromosomal exchanges induced by heavy ions.

Heavy ions are more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. We measured the induction of complex-type chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to accelerated H-, He-, C-, Ar-, Fe- and Au-ions in the LET range of approximately 0.4-1400 keV/micrometers.

Biological effectiveness of accelerated particles for the induction of chromosome damage measured in metaphase and interphase human lymphocytes.

Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy.

Analysis of complex-type chromosome exchanges in astronauts' lymphocytes after space flight as a biomarker of high-LET exposure.

High-LET radiation is more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. To investigate if complex chromosome exchanges are induced by the high-LET component of space radiation exposure, damage was assessed in astronauts' blood lymphocytes before and after long duration missions of 3-4 months. The frequency of simple translocations increased significantly for most of the crewmembers studied.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding.

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.

Comparison of chromosome aberration frequencies in pre- and post-flight astronaut lymphocytes irradiated in vitro with gamma rays.

If radiosensitivity is altered in a microgravity environment, it will affect the accuracy of assessing astronauts' risk from exposure to space radiation. To investigate the effects of space flight on radiosensitivity, we exposed a crewmember's blood to gamma rays at doses ranging from 0 to 3 Gy and analyzed chromosome aberrations in mitotic lymphocytes. The blood samples were collected 10 days prior to an 8-day Shuttle mission, the day the flight returned, and 14 days after the flight.

The effect of space radiation on the induction of chromosome damage.

To obtain information on the cytogenetic damage caused by space radiation, chromosome exchanges in lymphocytes from crewmembers of long-term Mir missions, and a shorter duration shuttle mission, were examined using fluorescence in situ hybridization. A significant increase in chromosomal aberrations was observed after the long duration flights. The ratio of aberrations identified as complex was higher post-flight for some crewmembers, which is thought to be an indication of exposure to high-LET radiation.

Chromosome aberrations in the blood lymphocytes of astronauts after space flight.

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions.

High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase.

Purpose: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure.

Materials And Methods: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture.

Comparison of F ratios generated from interphase and metaphase chromosome damage induced by high doses of low- and high-LET radiation.

Although biophysical models predict a difference in the ratio of interchromosomal to intrachromosomal interarm exchanges (F ratio) for low- and high-LET radiations, few experimental data support this prediction. However, the F ratios in experiments to date have been generated using data on chromosome aberrations in samples collected at the first postirradiation mitosis, which may not be indicative of the aberrations formed in interphase after exposure to high-LET radiations. In the present study, we exposed human lymphocytes in vitro to 2 and 5 Gy of gamma rays and 3 Gy of 1 GeV/nucleon iron ions (LET = 140 keV/micrometer), stimulated the cells to grow with phytohemagglutinin (PHA), and collected the condensed chromosomes after 48 h of incubation using both chemically induced premature chromosome condensation (PCC) and the conventional metaphase techniques.

Tumor necrosis factor as an adjunct to fractionated radiotherapy in the treatment of murine tumors.

Recombinant murine tumor necrosis factor (TNF) was investigated for its ability to increase the response of a murine mammary carcinoma to fractionated local tumor irradiation. When tumors in the leg of syngeneic mice grew to 8 mm in diameter (268 mm3), they were exposed to 3, 4 or 5 Gy gamma-rays daily for 10 days. Tumor necrosis factor was given 3 hr after each irradiation at a dose of 2 micrograms per mouse.

Adoptive immunotherapy as an adjunctive treatment to thoracic irradiation for pulmonary tumor deposits in mice.

The study was performed to determine whether local thoracic irradiation (LTI) causes accumulation of adoptively transferred peritoneal exudate (PE) cells in the lung and whether such treatment improves the response of tumor deposits in the lung to LTI. Tumors in the lung were generated by sarcoma SA-NH cells injected i.v.

Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy.

Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v.

Sister-chromatid exchanges in mouse embryos after exposure to ultrasound in utero.

Mouse embryos at 2 stages of development were exposed to ultrasound. The bone-marrow cells of the mother, the whole embryo, and the embryonic liver cells were analyzed. There was no consistent increase of sister-chromatid exchanges.